nuhammad lsmall

Irohtion rnd StructE!'e Elrcidrdotr of Bioxtive 

Metrbolites frofl li.rr$paz c.irpa 

.nd 

Applicraior ofNrcleophilic Cralblir to the AsyEmetric 

G€rerrdoD of Qu.tern ry Stercogedc CeDtersl 

Tow.rdr the Formrl Totrl Sytrth€d! of (+PiyroctigDire 

Tr..i ofti. D, |ffir h tlh|d.a6. R.{tffi!tu n IrqE 

DOCTOR OF PHILOAOPHY 

(Ch.n|l.try) 

BY 

nuhammad lsmall 

tlei!E tiirrrrl ls$ htrdof€ky, 

InEurioDl Ctu l|r ar@i..I ud Ek'loaicd S.i*.3, 

u.i6ry of K-chi l(rIii752?0, 

P.lift 

2009

Ded,ir hd./tu ntlrd.oyeA,parc tt 

Broflwr& Stt&.rt 

aad, 

Tatlv,r* 

wil*vlaveand'afle&ro*

Th.si! C€dficate 

Ttir b to oltry |h.t ,! fB! .did.d, "b.t d.n ud sttlcn|D Elctd.tion of 

BLo.clD r-Do0.. tt6 rrr.po .rrf. .nd Alttioab. or riFbo9t$r. 

Crt lFL ro dr A.yt finc O.ftdnor or aqbridy Sbrosdh C.it * 

lonb o|. Fmd ldt aF!|-8 ot (-I+ty...dgntF-. h6 b.dt .ub.nitrld by 

Mr Muh.nmd ledt to th. 8@d ol AdrdE d Sn/dy .nd R4.Eh, Unis.it, ot 

rotrdri br nr md dl !r d.Co ot Doctd of phito..riy (Chdt!try). H. qr*,d out 

hb qd€r dr &p.tot*h. TrE 

'rydr 

dt nt otlhi th*b, htuIrInpdrt, h.s ior 

!.&r &brIlld lo -, ots tEn'tui. d uni6ity ld tlE .wd ot dy dlcE or diptoma 

Pirt Di Arr {.&hi.n *. r'. Hr. sr ' 

tt^-*- 

ProL Ir.. f,uh. !||d lqb.lChoodhrt ar s,,rr *-t'?i' ^ . c 

It E t ta.{a Isad& of Chdttbt 

Iad.4 cel* Cad..l..a rbld.a S&4 

v,r,81' { ruehl rwra75274

Tln l. Evdu.tlon C..tlficrte 

Thi L ro arty rh.t nr ln{t ot Mr MdEms, ted qd.d. "robdon .d 

atr&tl. El!d.rd..r ot Eb..dti tffi ta thoaa ..t p. .i.l 

ADpllqild ol xEhorallk C.bty.h 6 ln. A.ytri.rt c.an!.. ot eun t 

$r.t rlc C-r.r lerb dr Fdrd Tod qinrd. or l.)+ir!..d!.a.., 

&p.ivl..d bt tu Dr A!r{-Rd'h.n (Fi8), r,ror. M. tqb.l choudh.ry.nd Dr, ch't J. 

RLrEr. ha b-. 6d!dd dh F.ii'. *Er. t' lh. trdrE ||dry rsnb.n oa 

tt.H.E J. R.-d! trdtnb ot ClEi.rv 

ro, Or. \/.rq.r lrdrln Alur.d xr_ !r 

P.oL Di B||t !. Aid.&d s_ rj 

Pr.t Ot KLmr.|(lln rr 

n Et raed k neqfcaer, 

Ie C.'et* Ca',.'l dtb&rr.JS.a.6.i 

tu."t 4 r--t! ttr.L7t24 htn.

ta-----i.at--*Lt*-tt-A 

rt-rcr-#a.ll* 

ar-F.,!b.-ir-a 

l.li\

(0 

(iD 

(iir) 

(iv) x 

1.0 Gdr.l l!a!d!dio! 

l.l,l M.diciMl plals a a blE of n.w ph.lrueuriels 

1,1,2 Appliqtion of lhnt.dlcts in r,sr,rcnts 

LL3 Clobd baine ofortu l DlrdB 

LL4 RoL afndiciml.hemislry in drug d.v.loDnsrt 

Ll,5 Obj4liles ofth. ouftnr srrdy 

Irlr.dxlior ol thogDro .rirrd 

2.1,2 Trslition l dd ndicin l ss of em. plmb of g.n6 t ropdfu 

2.1.4 EtJ@blisy oa Tiwpda ctitpo 

S$ld.ry M.r.bo[... oa tlrNzm .rtrr! 

2.2.1 Cl.md,Ft?.fuasdiidFnoi.Ls 

2-2.2 Alkloiblonsitldtr 

2,2.3 PHtoB itudid on Ti@g)ta.ritq 

2,3,1 Bios'nlh6n of clqldoet !€ fmodi&D€noiG 

2.1.2 Bi6tnd6is of +orPni* ad qdin..lk loi& 

l1 

t2 

l3 

17 

t1 

t1 

l3 

26 

30 

12

3.0.I.ibtior ud ChDclelation of Ssodrry M.l.bol,it6 fro6 ni6pt ehpa 

l.l,0 Rad! ud DLuiotr ll 

l.l.l Cfebdtrd$pe tudod'ceoroi& fton fa6ptt. obp- 

3.t.l.l N*@niudts 

3,1.1_l.t RuBphiol E O) 

3.1,1.1.2 2-Hyduybodp.bi& C (t) 

l.t,t.t-l Ti@isposid. A (l) 

3.l,l.l_4 Tin@isFside B (4) 

3.1_1.1.5 Tinqisposi& C (5) 

LLl.l5 Ti.gispGi&D(6) 

3.1.1.1.7 Tir6ide A (7) 

3.1.r_1,8 Bo€Cd6id. I(8) 

Lt.l_r.9 BGpd6id. r (r) 

3-l.l-2 |

3,13.1,1 Psdft(21) 

TabL oJcont rlt 

3.1.1.1.2 x-?}@&Dloyl 9Mirc (23) 

3,1J.1.3 MetiryH,,l-dihyd6xybqleie(24) 

3,lJ.l,a qridi@(29 

3.1.4 PnqE66.td tilapaE fru tbdporroirpt 

3.l.l|.l l

32313 

t.231.4 

3,23j5 

3,23.4,6 

3,23!.1 

3,23.4.3 

3.23A9 

r23JO 

323.5.1 

32l52 

323j3 

323.5,4 

3.2.3.5,5 

323.5,6 

323.5,1 

323.5.8 

,l"l IDdrlorodlLtoly Asy 

4.ll R.oltceddi!@io! 

d2, Isllr.oddigehd 

TaU. tcortqts 

it-Fomyl&Mru|ulirc(18) 

x-Fdy'noruirdiF(lt 

X-Dd.dry!ffdryLldj/dmuituic (tO) 

ir-D@.&oloyl it|nirc (23) 

Mdnyl3,4-dihyd6ryh.Mrto (21) 

5,?-DlD/d,!xy-2

at 

5J 

53 

5.6 

5l 

Selio! B 

t0 Appb.rriM or NlcLopbnic C.tr\trit ao O. AryoD.tric G.!.ntio! of QE.t nr4 

Sl.nog.ri. C.rt 6t Tos..d! tb. fotu.l loitl Syltleis of(-)FPbytdtlgnin€ 

5,1,2 NucbphiliccMlysis 

5.1.1 Chiml nEloDhilie d/C-..y| r&lfcr c.ralyis 

5.1.4 Qu.tnury slrE8@ic et6 in ltm.tsic stdh6is 

s.2.1 SFlnsis ofohid 4-rminop"llin. nuolmDhilio @lysl sd sEps rowards rhe 

trthesis orclphrsoslismin 

5-3.1 Goeal cxp.rjMbl pre.dls 

5.3.2 Seps inde synlhdhof chnat rucl.ophilicDMAP@t lysl 

5.r.3 st.ps in tl'! fm.l toll srr nsis olclpbeslisnirc (99) 

t51 

153 

t6l 

163 

I65 

l7l 

t75 

185 

t88

FiRt &d fom6l I oFq bJ' sim.6t Snd dc to lh. avolulion ty sicnrnt of P.losra4 

Ptul Dr. An{-Rthnd /.Rg N r, H L, s.I, r I t lt Ptuvidine excellcnl eientific facililiB 

at $c ICCBS. His vision and l.ldcBhip tud. Posible 

to ltsfom the H- E- I R6cmn 

hstituc of Cb€mttry inro & itrreblridd @rer of .xels... tt is a sl@ of 

notivation md symbol of hopc for lhe .nrie &,tid. I cmd thatk hin 4oud for 

allding re to h. . part of lh. gr.dtBs that hrs Gdh gtoup ba &hieved 

I would like to cxpress profomd ehdnd. to my @{!Pdis, Pbf Dr. Mlrl|@ad 

Iqt l Cloudh&y 64s,,r), for his invaluable supFr! encourageh.nt, supeFision ad 

uetul suSg6tions tleughort lhis 6@h wo& I will never forg€l his kind ed 

ocouRSing attitudc ed patienc. all fie timc. Ded Sii, this wort would ml hdve beo 

polsible withNl you suppon ad encou!8cm€nr 

I u dc.Dly indcbl.d to rny adviw i! finrl stagEs of thc {otL, Dr. Chti. J. Ricltd. al dE 

school of Chenical scimcd and ?hamcy, UniveEity of E6l AnSlia, UK, lor hG 

suidd.c ond l@hing in erpdime .l sytrlh.tic dgdic ch€mt[y. SPeial th4nic 8o to 

hin for .xbasdirary dd erdl6i 6wu to ss@ good polilim ir ny t.s€@h .di6. 

Ttis work wodd nor hav€ b€.n posible wilhout th. suppoa md d.owigen nl of Dy 

@tldgrcs dd Ai.nde. I m thn Stl to It Alb.d Alt . KIn for D@ dacsio ud 

guidecc s a soior collague. I m happy lo €xtend ny 8mlitud€ 

lo Dt $md Youet 

Dr. AAtu B.grb, Dr. Ali A-pb Dr, S.t.d J&, M!. Snn Mdd, MB. sof. K. 

Arvi, M.. s.iird Ali Mr. AD& rwio, M!. Sb$'n rlleio" Mt s.jo r:r Slyula Mr. 

Acblt Adtiicti, Mr. z€lid ll|ein S@tu, M! Mdu Bibi, Dr. Ozld Dditlc.l4 

Mr. M. A- SrlE, It M.nnd Odda Mr. Li,iq.t Ali, S.ycd Agn Eldi Mutw( E. 

M(r*i ed Mr. Ghul,@ Att ! haw ale b*n aludrntly h€bnn, sd hlE sisl€d m 

in nul]@us vays. I .e't forgel lhe ssislar€e dd sflices of our l.b. atlqdet Mr. 

I would lit€ ro !r&* ny collcls@ &d ftiods al ilc IJEA, Dr. E!d. Bqsi!, Mr. 

J.Ir8n Aii4 Mr, Chri! S.b$dq Mr, Er0id C!r6f ed Mr. ,@.1 for nice compmy, 

suppon dd gui&rca I vml 1o cxrend Dy ghtitude lo Mt ftli6 E6e for naking 

sonc dclicious Fench dish6 dd prcvidins nice conpdy at l4Noddg€, UK.

I would 'bo lik€ ro dr.d( the B.nilh coE il and Eigh.r E&.|tid cooni$ior of 

P.tit! for lhc a{ard of th. Sbqr Tm Ph. D. RB.eh A!..tffil Felldship vhich 

hs suppoilcd De duing Dy six nonrhs of B@h in UK I would like !o thot nv 

suFdisr PF[. Dr. Mol@d tqb.l ch@dhy cgth to mhinde trd facililrte sd Dr. 

C. J, tuohr.di for guid&c. ed eceptdEq for this award. ln addition' I m slso indebted 

ro Mt . B.@ Ayub R..tib.!i l&. Lloz.b Xbn and Mr. F.bl II t@ fo f&ilit tinr ir 

g.ding Bntish visa, Eugercnls for ihe dwdd c*mny ed for timelv htufd of fiitls 

I rculd likc io ihel Dy d!.tis 6mide fd lheir inv.lublc tin€ dd advi@r Ptut Vhd 

!ddi! Alnr4 Plo[ Bid S. Sildiqri ed PEt xb.la l,t K!!- My uiomst lh@k al$ 

sds to the f!4dty m.nbd ofICCBS, Prel r| Btltt, Prot,1" MdiL, Prot 8. r8izi. Dr. 

s B.a|to, Dr. s. Ali, Dt ls Sht ald Dr. l. Std.a for Ga.tina drtr.ml @llg I 

would ,lso &kmwl€dge dl the i@hnic.l .d not-t chnicsl llaff of the IccBs for ihc'r 

$!'pon in Fording NM& Me, UV tnd IR lpocla .d si.fi Mbds of libErv 

I ow! vcry nrch to ADf Dr. Nordin IL lin fd poviding pld extr&t from MaLvsid l 

d a1s thslfin b Di Mubmrd A- Md.ik for condetilg imulmodolalory Nav 

and Mr S.uid A, S.ta.t fd c'roroxicity ,sy, rpon d in Fv dbs.nalion 

would @r hrve b€cD a 

My dlys dd ridls in lab. ed at th! Gid.ncc ovd l6t fiY. v€d 

cnjotlble .!d 6 dt{r.t irirg withqt |b. haltty corqdly of all my collagud .nd 

fiiodr ar $e H. E. L Boy s Hdtel, 

tsr blt not l.!sl, thels to .ll mmb4 ofny family, esp€ci.llv to my nolid Withoul 

her coNrant, *Ifl*nN, ld. &d pdy€r\ I rqld rct b. hdf the Fttu th.t I m knay 

I hoDe that I have nadc hd preud, rnd thrnl hd for everything she ha donc fd m. I 

ljmt qd wilhoul tlarking ny f.th6 Ut Ali R.$b.r, nv bolh.6 Fid. Itudj4 

Mrfi.m', Ebrihru dd Ilaidd Ab6or &d siste6, Fdi,o. &d S.l.aB fot fien bve 

support @d p6y6 ir dc.y 3Lgc ofDy [f€. 

t( .0 

Ku.ti 2!0t

I.tFd&dor of Ph. D. R.6EL Sctlohr 

I B hon iD dhlricr Gilsil q 22 Auslsr, 1983. I lrrn d my 

.dEtd cr PiD,ry Sch6l HoF lo 109a, I mv.d b Hkh 

S.hdl N.8rr tm rh@ I @oplct d 6y SSC (S@&ry 

Sch@l C.fri6@t) in l9?. I *.r iltcBlcd ii brological 

&imrnidnod}tr.dn.bnt .rlDisi@irFHn dic{.11h.D.s*C.ncleGnrn 

tm c r !o!*d dy sssc (Hisid sqdq s.hool caiitdtd) i! 199. r B 

d.t mined to g.i hiliid.{nrqdonjut aft6 i.taE.dia!.. I Ph!..d ro Cict ay B*n lm 

d.e@ E@ th. hrrd.nr of P.!ir.A (!@hi t Ft 

d by &.&l@ itr s.i@ (s.sc) 

wnn Cn@isty s . rrjd i! 2002 tr@ UnndnY of xdli l.ttli.d fd artdiatoa i. 

lvtsrq! tbrugl' Didroare of F4{.dm Dtt'd Gilgit .g!dt 3Fid.d qDta sb it 

diftGr Univ6iri6 of Pr*j.t0. I I &l€n d tu .tui.i@ i. ih. Glful thittdtv, 

Dd l@il KIe I ajoyld tb. @ de vEy tan &d qFidc.d & o@lLd 

l!@irs dvibnr@t h 2(x)4, I $di6cd wilt M.S. h dgdic di@isry win uPP! l" 

divi.in od @a.I t'poririo.I w ludyro g.1{hisid in M. 

'l! -/I,L D FDlm.t 

.t Ir E. i. R.gt! Iriitrr. of CiEi*y, vts! I va .si! fc@L ro bc llc tdl 6r 

dEd.d R rch gdt ofPot Dr. Allsd-Rlhdd sd Pol It !! Iqbdl Ctddbdv i! 

April.2005.I u asrtLd SlaA (sbdt Tm PL D Rtrh atE hlMO &lloslhipbv 

tb. Briti,l Coeil erl HislE Edrni6 Cdrisit ofP.lino fd. drd.d .dt@ 

t!3@h i! uK !r lh. Uni6it of Erd A4lir 

ln rhe tun&, I vodd lilc ro €diN ny Fsesn *irb al ..d dnui@ lo hrirs 

imowd@ in Choilty by utitzi4 rny tuh ap.iq* dd lo@Ldgc l wil! ro 

Fe ny l,6 i! rb nd& of rrddic drei ddift a *dl a rhrl F!.ti.t 

ch.oblry. r u vay 6.eE to l@ .d .xt d oy *iU! ..d 'd@ttdinS! it lh* 

ndd!, Rcs4n !ffi.ndi.txl *idE d6 t tt@ it ccte It Gqun6 pdilc &d 

oin@ dd I d Edy fd i!

SUMMARY 

-the disendion is divi&d into iwo s€tionst stioro A dd B. s.clion a de$ribs lhe 

ielation dd st!.tN clki.ladon of tw6ly nine s@trddy mc|alrolitd Aon liMlo.a 

..tupa. h ale dcsibd thc ctioloncig .!d im@onodulatory 4iivni6 of th. mjot 

netaboliies of lirorprra 'ir@. Salion B desibes th€ applicalion of nucl@philic 

daiysis (o liie 6'1fueric gd€rarion of qu|mry sl€Eogdic.{16 and fomal total 

synrh.sis of Cbhy$srismine. 

This pan coDpnss phtl@hdical invcsligdioN oD enal p.ns of Tinospqq ctitpa \L.) 

Mi€6. It inchrl€s ielation dd stnature .leidatiotr of dn€ nd r-9 Gi8. l-2) dd sir 

rtus l().l5 (Fi& 2-3) claldac-type iluodirdpenoi&, .long with a tr* apoDhi@ 

alkdoi.ls 16 (Fig. 4). This sludy yi€lded fiv. trou aporphine a[.loids 17-21 (Fi8. 5) dd 

two lytuin€ dkaloiG t2 ed 23 Gie. t), Thc olnd krom co8tit@6, islarcd ftob 

Ti@sporc .ritpa, iftlude Delhyl3,4njhydrcxrbeierc @a), c}{rdDe (15), syrinsin 

(26),5,7-dihy(Lbxy-2-(4-hydDxyphcnyl)-41l-l-b€mp'm-4-onc (24. crcteucale.ol 

(28)md3-Cl-D-glucopFdosyl-r{itostemt(29)(Iis.5). 

TLe isolalion of pl&l sn.bry n€ratolit s &hdvd wirh rhc help of nomat dd e!@ 

phe chomiognphic tcchniqucs by Ning silica gel, poly-mide, Diaion HP .20 resia 

ODS (RP-18), S€phadex LH-20,.1c. Prcpdrive H?LC (L-Eo, M-80 ad H-80, tH ed 

2H, CS.l20, elc) @ u.d for 6n l puifi€rion of @npoudr from builetic exF.cl of

Thc ct]@tedarior ad stu.nr! .luciddio! of pE onslihEt|rr ft8 TiMspM qisq 

w€re 6icd oul by Bing 6oded sp€trscopic l. hniqres 3wh a MS (El, HREI MS, 

FAB ('ve). lA! tve). HRFAB Ms, ercr, lD End 2D NMR llke 

rH.NlvtR, 0C-NMR, 

HMQC, HMBC. COSY, NOESY, ROESY snd TOCSY, ctc- Singlc{rysral x-ay 

dim'aclion alalysd of crFtalile co!.ditent!, d sdl a dedvatiz.tion oa som. of th. 

@mpouds, wE al$ @icd out fd lhc ftrrh4 @nfid.lior of then stretm std 

srlMc!€disit. Th. sf*nc of @ aid L@m satrdut r|aat6ltu9 noh.d fiom 

Tinosp!ru critpo, arc pGsn!,l. 

In addnion lo thc air@tual snldy, immonodulatory ed cyioloxic .ciiviti$ of Mjor 

@n$itl6lr, ielaEd Aom EIOAC ed,-hOH t!.tios of Lespola.rirpd, vw abo 

r) Nd ud Xrmr CLrodurtyD. tr!ruodla..D€n. L.cto"6 Itum Tl,6pM 

! 

aIR' 

P 

H 

oH F(tlal@tlreyD EH 

oH F{ADslrcopyrdosy{l-6){-D-xyl*) o-H 

{ X&t!S[,cot't0.ql) q-]l 

Fig l: New cl€b.Leryp€ nllMdi,arpcre l*w I1 fro6 Titusporo ctitpa.

ofi a-{ADgh.o?rrGrD Gn 

H F('.r}sl ,..sE ryr) FH 

d-(&Dsluc.ryruoql) crl 

() 

-#" 

tr' 

fi& 2: Ncw and tnom cl€rodrnetyp. firramdiLrp* leton r tl3 fto6 T. oispa. 

l3

2) Klom Cl.dd.n6lt?. Funrodit r!.n. L.ctordr ftti liM?rro.tlt 4 

t4 

Fig. 3r Knom .leDdu.-t?c nlfudir.rpcre lactoE lcl5 from tl@P,/4 ..ltP4 

3) Nd ADoahin. Alcloid! freD riaolpfuc.sPe 

.".C.toS4-"y-.) 

*oir"r" 

U" 

l6 

Fr& 4i NaapoDhin alkaloid 16I6mnrcsporaoiw

4) Xldr ,{Frplbe dd TyhEi!. Atlrloih Alolg wiih OO.l Coutitr.lt 

lrca Tt 64rt crlspL 

{ { 

,,^c-"0^-ef- 

A 2l i" 

. 4-{'" 

*yYJr-J:-; 

I '6* 

to-l 

Fi& 5: KnoM alkdoi

S.ction-B 

A higbly dliv. ed sel4tile chnal4siFpttidb. nwlcoPhilic caLlvsl l0lt (Fig.6) s6 

synthcai&d in thF3tcF filn olreEidly aEihbl. h.xue-2jdim€ Caralvst r05 

B $.d in tL sleEli.h @rrangdcnt of c-eyLLd azb.lo6 (up to ?6vo e} Duitrs 

the pGdt s|udy @6tysr lO5 is .ppli€d b lle fomat st1met rc svnthesis of G] 

physoniSlnrc by irornhion of m all @bon qut rndv std@g.ni'. .entet vio o/c'evl 

tl1]fugm.nt A ket ptelNr r20 s6 also synltr*i2ld fm tlE 661 lim' apPli€d fo. th' 

svdhesis ofa wide dgc oi biologically impondt Mtunl prodrcls of indob tr€bbn The 

challenging st p ir tlt€ iot l syntlsi! of C)-phy$1iernire wd @mPleted in >95% 'e 

Htu th. eMliosl{tive fomal rol.l s}atbdis oI G)-phveliemin. 

h cidl steps sirh d ovcall yield of 56% (@Fini2.d). 

*-,ii* 

(99) E @npleted 

*U""_'n:*C+*J#Cry; 

'" ".*."."=;o*"*. I 

R= E! !x R=qoqFcrr!6x I 

| 2 sr'P{ 

I 

*"*-r^j(-l," 

G)-Phylonismire (9) 

'r.o_,zr.y\ -c 

IFo 

\-^N 

Fi& 5: Applicalion of csLlttic €Mlioelelivc O/C-&yl !E tugddt to the foml io1ar 

srnlh6is of Clphys3tisrie.

Cf &v,,t 'k L! -trt n o' -;ttp :,/2at -i\t2,+ 'P1ol vf/) 

L orl. / Lt, L G,r' "!t G z,r' -q l l,*- rnospoo dispa ? ?../oV 

'J - 2 e! {'! 'tV tf '!J( inmunorFdurrtorv ,r caioroxi .it 'G -V? iV? 

4t ry& [ phy.ostisnilJe +i L 'f { // at,( crtiBt - '' '! A f nocr€oPhiric 

-ltP 

-+,{,t 

-a a I L f,,t';,.ta i/l( &v { t. oispa,4d uatavs|aa.o 

" 

&l.t 16-17 z-",)?,darcdanclypo tuEnoditerpens,? (P 6't r-9 a- i - 

-z-''!v i -(t,' fj.-t * 1 r':V.It -Lt rf, aPolhine atkah,ns,t l' 

,i,fL F -'.1-n ,yL i n N, fr, 27, a, a ,J? tranine alkarokts,lt 

^ 

.diaion HP-20 .silli6 06r d ci -{ q-f, +" L Jet L 

'q,, 

,tt 3 -P l-t rr 

/-tr. tf,,.f I vep.,at*uptc -O tJ6'/!'sephadqLH-20 ,oos (RP-18) 

-{t{JE?tt'}A& LuvA; 

.t )E /,)k.,'.e )J"L Ja -p di, t) J..'" Jy' 5 ={/ '}.r. F 

n/-va" -d?-wgL '! "t,t.r i.,zr,uuat,y'c/-v,J//.r tt -['! tt 

,,1, 2a 4 Jv Q tlrq L/,t!t .' pq f '-ti,,e.r,}tst Jg .,t d,/u, ,(zo run) 

rlt{i),Q} 

2- ,J ,tt .tt +" L &l iU? immunornodul.iory ,r cybtoxicltv ,& Z !,4 

-{{< ('!-{tt-,' 

naxaae-zsaone -. tu I ,) t'/ ns;5f 4{t € ," I e14.t)vo 

iv L,Jv(& 4.,y6 { eny.

GENER.AL 

INTRODUCTION

1.0 Gf,NERAL INTRODUCTION 

1.1 Introduction 

Thc nljor pan of the cllmt study foclM oD lhe phttchdicd iN5:tigrtioa on a 

6c4icin?J plu\\ TitusPora uisPa (L.) Mi.u of Mtlavsis otiEin This ha l'd !o thc 

ieladon of evqd rew 4d t@M cb@ical @nsinmti *t!ic[ q@ walul.d for dci. 

imwnodularory etivity dd cy&tioxicity .lT€ct ag.insl both mq (PC-l) ed notul 

(lTl) cell tifts. FoUowitrs is a bri€f wit -up sbout lh. impollde ofn€dicinal pldts in 

do8 di!6vdy and d€v€lopn€ni, s w.ll s lh.it ot. in tadidonal hdbdl n dicind of 

l.l.l Medicinal Plarb s! , Sorrce of New Phrrniceuticlrs 

ft ha ben l@8nizd lhal th. pldt ldlg&n @ntsn & @moE dilc6ilv of *6i&rv 

m.1aboln6. Irdividual ptan sp.ci6 @.|!b tho@ds of EiqE bi@h.mic.l e iri.s 

.all.d enzymc. Tn * enzynB play a k y olc in lhe produclio! of thoMG ol 

conpouds in BpoN ro dy slimulN [Fmwodh, N R, et ai, 1985]. For etupl.' 

plets gbw ir hdsh clinali€ mnditio. ond hav€ a divds tugc of seco.dary 

m€iabolitcs shich h€lt ihen to ado ro .limatc coditions Th€* gldls &veloP d 

.xd@di@y @y of deGre b r.@ of cLnicab lblr Ptut*ll 

1hd ton vital dr*l*i 

nfgrl p.lho8Es, iIgts ad mli& pEdlioR This is eiv dcry lim. . PIdt is 

invdisr.4 tr* ad @€l *lEnEs !& disw|td ftis Nleular divc6itv 6 bc u$d 

for ln. ddetopnfrr of ph!rclri.ds for th. tslrtr. of hllm diws. L b.nit6Ld 

$at th.r. aE mus y 500,000 hi8ls flowiinS pl&t sFci6. @cupvi'8 $c lcftstial 

h.billts [FatrNonL 

N. R, ?r at, 1985]. out of th.m, ody a few have bd studi.d for 

th.ir medicinal con*inroB e'hil€ th€ Maiojng d€ u-es@h.d nysteries for ei.ntisis 

Only l% of $s s!ei6 bave be€t lhobughly inv6tigatd for their nolel lhcapcuiic

ag6ts [&on' 1992; VeL, D. J.H-,4 aL,lllg2;Mtlilltrl,c,et al, |98; Burld' M. s, 

2OOll. De$lopmqn in th. t.ld of.rtunl Poducl cldistrt ha bocl€d incrat itr llE 

nldy of norel plsr oebbolit s with polmtial rh.dFlric value [Fmaonb 

N R erar' 

l9S5l. h is mw rccoelizd thtllh. strutusl divdsi9 foud in F$ral PmdEts is a 

uiqrc res@e for tne di$ovcty of rcw ddgi dd othd biologic.l atiti6. UFlo dale 

aboul fifty peEdt oI all p6cdb.d dNgs d€ cithd ddjved fem natual ptoduls or based 

on nalural prducl sltuctws. Thc availablc sm* fm $ch mo nns includ. eitul 

pldts, {d nicro{rgdis oflarcstrial or ndin oiSin (Mahidol,c...tat,r99al 

t.l,l.t 

Modcm M.di.i.G frur Hid.r Pl.lrt 

Medion,l pldts play ! lcy rclc in |h. d.v.loPnc ofncs m'dicind fot the !E!h'nl of 

dis.g A nDb€r of plsnl b6s.d n4 &!gs d inuldu.cd in the drug @rt€r €very vd 

[vete D. J- H., e, ol, 1992], sNh s dsrpidim' Bit|t@i'e' 6e+rE, vinbhsrire 

Epdycin and vieislift e vdy Gffalivc nalual ddrr, available i! thc o'net Gig 

l.o. 

Pldt-bosd &ues bave 6a

In rlevcloping eourii4. medicilat pl.nts remin the main $UM ofDedicado$ lr Chini 

aloft, ?295 pl&r spoi€s m utilizd s ncdi.in l agcnis [Mslidol, c, et ai l99Sl Tlt 

Wotl Hcllh orgeizali@ (IVHO) ts dtimtd t!.t tlE medicidl plrnts s€ a ln' 

FitDrry ellc ofncdicic itr tL. dtElopiDg vo d Mtl ol, C , er dl , 1998; Buda' M 

S,,20011. Abour E8{/' of 6e wld's iihsbitads Gty minlv on ttditi@l ncdiciG for 

a s o|l d 

M ii o|l N 

o 

,.(^,1*.^-(.^.,(--.""

fic. 1.1 MediciBlly imPodrnt Mlural producis. 

Thft s€ r€porls tbal 6t lc6t ll9 6mpouds, daived lisn 90 Pl$ts sp€ci6, d€ 

iDpotul drugs cwnlly ued in oe or noc duni.s [Malidol, c , er al, 1998; Bnd€r'

M. S., 20041. Ofth*, ?7% b.ing dcrircd 8om pl. ! of folk m.dicinal impon@ lt is a 

fet rh.t in 1991, ndly halfofth. b.n elling drugs wE cilh4 Enr.l prcdwt3 or $€n 

Duins l97l to l99O, n4 dru8s $ch s gi.k8olidcs, ai.nisinln, dbilore. A1 

ctdydMerabinol t !ipdid!, *,lop4tid!, E- &d Zgu€gul3tlloc, ald plrlnoiol (Fi8 

L | ) *ft dcrctoD.d tlrclgh . tsluidEy *o* i! mnltl Fldu.t ch@krlv all ow tb. 

srld. Abo 2% dols of Mtunt oiiSin gw ilrod$ld duing 90t' i*luding p.cili'*|, 

ropr@. smislin, irinotdD cr. (Fig. l.t). 

l.l.ll N.tunl Pr.d$lt u Adi4lcr A&!L 

Aps Am b.ing e de[@t el@ of eti-hLctios dDg!' Plnts & d$ go.d $ua 

of eti@crr !g.rts. Ntdond C!|E ltniu. (NCD, USA, ba hdLd u qLdirc 

togrm fd l[. dcvcloFmt of nrEll prcdo.$ fd lb. bhdt of vuiN fom of 

qtl6. Moy clinidlly efirl (|.ugr h.E ha di$dqld drdgh NCI .ffons 'I!a' 

iftlud. vinbf.niB r"l liMidirc tod Cdtua, s tes' &d tbc si!rynildic 

cloposidc, nrcl (Fig. l2), {d 0E misyntlFtic iaxot4 [M.hi!o[ c.'., aL' 198: 

Burta, M. S., 20o4t. Tel b oE of ln. b61 .nli...IE .s.nis thd ha bdr islatd liom 

llrcb.rkof rhc Peific or Andi@ tN t6,T@ bev{olia.'tt di$ovdv oft xol h4 

drr&r.d.t!!jor int Bl of q8@ic chdists i! PLnLdiv.d 6tic.|@&!8p 

1.1.2 Applicdioo of Phrt Ertrrcat in Tr€rtd.ntr 

h is aior.d by tla Vorld tt rlh org&ialid (WHO) tld ,$mxin t lv 75-E094 orit 

mrld's popul$ron lg Pta ncdicine€, citlt ( i! prn or otilllv lPatsadhlt' 

B., ,r dr' 

2oo4l. SiE 'hy p6plc camt.flod th. hish @5l! of nbdm d'rll@uticd d$gs' 

rh.y pElcr ro & pl&t cxEe!' A gtowbS ndbcr of Ahdi@ @n6Md 4 $rniD8 b 

Dldt nedi.incs for hey |!es, trch s low @si dd n.iutal ali.dEtiv* vith f.wr tide

cfcds. chin* tiditio!.I mdiciB milly bsd otr p|{t .xrr&ts e G.d by lqse 

chitE popuLtior ft. vlst Eljdily of plat *!i.t3 N.d it Cbri* ncdhiE h8 no* 

ben buld io tsv. llcdFutic .ff6r* Tt. tlditioDl syr|tu ofndici@ in ,.p{r k@M 

s "K,DF", i! u ldlplrliod of ChiH. ttdilioul mcdicirE. KeF fomuLiodr @ 

multiqbpoMr nixl6 of dtul prcd@ts, p.iNily Plt dl.*rt lFffircdlq 

rgEEl. 

l.l3 Globrl Bu!i!63 ofN.torrl Pmdoctt 

N. R. 

Aboul 6iny Dd @!t of rh. bddvi& !.16 of drug! !E b6!.d d lal6al predu.t. TIF 

\r'Hq .nq @snizins 6c ib!o.i.D oft ditio!.1 m.diciD., hls b€r &iir in qa!.s 

sllLsics, gli&lic &d st&dnd. for th. Fot6lion of labd n dicic. Som of lhc 

FrEiffit pbrl{dird o.diciol .mpo@dx i@lud. @lchicob, @lchi.ie, b.iulinic 

*i4 @ioth.ci!, 9+iinocatntolheia A!p.toF, LF.iol, d@t r@1, pa.lir.r.l, 

tut@@i*, pildlrpirc, $.pobnin ,.t! 

(Fi8. 1.2, P!se4. 

TIE lotal stc of phytomcdiciB sl. E?on d i! thc E@per UD@ sll &our Us 3 6 

billion in l9l ard $ 4 billion in 196, of *iich rlm3t half lw rold in Gcmlly (l 3 

biluo.), with 5.16 i! Fd*c 3 1.6 bilio!, ILly t 06 billid ed h9.. I Lt bilion [veL, 

D. L H-,.r.1., l99t Mlhidol, C.,., d, l99El. Tlt F*ot glob.l !Et!t t eid io b. US 

250 billid. I! I,di.,tbc !.1. of bbl hdt l podul3 is.didLd to tr I I bllio {d dE 

.xDon of habd 6rd. dE cB i!.bod I 80 niuio4 of siich 5091i3 @.tibt ol by 

.ywcrric p@!cdi@ [vcal., D. !. H.,.t al., 1992i ANt., 1992]. Pl&t d6iv.d Md 

d gs @ ihpon.d by sw..l coqrdB fd Nlgc iu tn liriotul D.dicin l pl.FdtioN. Th. 

lisr of@utie iDponils hclbd druss is !|.scntcd in T$lcl.l (PascE).

In Pakjean $ee e hudFds of htlb.l fomulstoE. tuuf€oifd by ditremt 

pnrmnanicil 6mp6ni6- Tn fmoB hat.l fomulado6 inclutlcs, B.EGla (tf,ro 

oduda),2Afr6 (oM satiwt S||aJiEa (Fuwid tttdicz. F Nntlo4 F ofrcinrtsJ 

aad SM&A.mL l.Argx.ia spect6z), .rc. Tic mjo. suppliG for th* hedal nedicircs 

e Hddrd t lontoria, Q.6hi Hclbal L.boEIo'ies. Metata Natlnl R6emh 

Lbohloies, Hdbal PM€ss, .tavaid Uo.i ttbonioriq ed Herbal Life, e1c. 

X" 

"in 

i 

r\ lr- 

Fb, lJ: c(,m*ialry 'vrihbL Dodl Drcd@ in rh. ph4medic.l n&t{. 

Commially, the plan1{6ilrd m.diciB @ wrlh alo US S 14 bilion. y6 in tne 

Unied s1als and US $ ,r0 billion mrldwid.. US citizG hlvc Eid d .stimr.d US$ 2l .2 

I

iui@ for wic.s plsvid.d by rft@dirc n dicine pE.tiliom in l.tc 90's A 1997 

swey drinal.d fiar ovd l2v. of adutt! h6d lsd h.rb.l nedicie duing 196, a 

c@p6rEd ro 2.5% in 1990, @ltirg b r tsilB of US $ 5-l bili4 LiUy R4gth 

Libontod$ Mkcls w.El nillion dolls wrlt of viturttim dd vinblstirc. 

TrbL-l.1. tlclb.l dtugs idrpotr.d by dioB @udri6 

india 

SouthKc - 

-r;;l;d;d; 

-.-- 

p.su8. of hs6.l drws hp.ncd 

10,5% 

!J%- 

L4% 

---- d.i% ' 

Fig. 2.1: Clob.l ph.lrll:dd.d elc. 

Yar ei!. progrs 

s&6 tMs H.!|m. F.aM'r r00a /'ldeo,E.360 abD.r Frrdftdrdr Fwlpdr 

TIE US N.rio.rl CaMr l$litut (NCD b6 $rauish.d h4. inirsttuclG to een 

50,000 naftlll subs&nes for activity ag.iB1@€ @ll lird aid l[. AIDS viru lv€alc,

D. J. H., er dl., 19921. ScicntiiB in Chh4 GcmMy, India md Jopa4 mong oilt€N, ae 

ale s.ding wild pldt sFi6 fd fte dsg5. It Edt phtme.'tical $16 ir glob.l 

mr.|.t ple is ple*nt d in Fig. 2-3 

t.1.4 Role of Medicin|l Cheniltry ir D.ug Developnenl 

Tddirionally MnDl podwts have play.d e inpofldt rele i. dru8 disldy, bll in dlc 

l&l tqo dccad6 of 206 6tury, @jor ph@@uricd @npdi4 has .ftnd t.miml€d 

oi $alcd doM then d$g di$ov{y pbgmme bed t n natu6l e@6, d.spilc lhe 

rer $d top 35 rcrldwid. s.llqs dngs in 2000-2002 l* @mplcGly b4€d on narud 

pod@B. Ituing rh. yd 200G2003, 15 Ee Mtur.l predFH.dv.d dfl8s *E 

intodwd in the ms*ct, elil€ 15 naturl produ.iddived @mpouds w in ph.l. lll 

clinical t ials [Bull.r, M. S., 2004]. Reently, th€ ph@urictt .onpdi.s 4€ showitrs 

cft*cd ior4$ in Dtural proder !t*4h ds ro lh. f.nm of dLhative {,$s disorcry 

m.dod. to ptuvide lcad @mpouds, s wtl d lo coF wilh th. chdldgB of.herging 

dis.5s s@h s imue rcl6red disorders, vir.l di*es dd nct bolic di$rd6 [Burl.r, 

M. S,, 2004; latwedhd, 8., et 4r, 20041. To codpele wirh othd dng di$ovdr m€lho&, 

Mlur.l lrodud $icfu hs adopLd bigh 3p..d mii8, i$larion, od sfucrN 

el@idalion techniquB. ftk B o y po$iblc by iltodeins h}?hcrul.d teclniqes srch 

s LC-MS/MS, LC-DAD-MS/SPE-NM& LGMS-Nl\tr, CC-MS along with hiSh- 

thrcuSlpui bioey sc@ai!! t€chniqB. 

1.1.5 Objectiv6 of Curretrt Study 

Thc ain of the c@nt sludy *a to s.eh for ncw bioeriv. saonda.y mer.bolites ftom s 

ndicirGl pler Tinspotu oiqp of MalaFi4 o.igi!. 'Itjs plad ha @y folldoric lg 

in $c Mdlysi& tsLn of n dicie. rrir lirdy ha Gultcd in th. isolalion of rhiny

@nrodds, including el.ven n w aad aiGt .n ttuM sondey r€taboli16. Th. most 

inpon d clN of @nDoud! oblain d A@ rnis pl6l is thlt of cl?r.de-lyPe 

{uronoditeryd€ dd th.ir elycosids. nF n.jor @nslittdB of th. Plant ke t€st d for 

im@bodul.rory &tivity.nd cylobnciy. Idq6linglt tLcs cdpou!4s rw fourd 

to b. nor-crroto*ic aeainst both fibrebbsr (lT3) dd prestat cdar (PC-3) ceu lin6. 

Orh.r biological $ltdirg! wE Nt pdfoE€d dE to limir.d q@!iti* of mq 

@6rirv sof nwrytu.tirya, 

The qlalttc gpnddon of tun-t..dic qu.ldrdy sl.@gcDc @l!!s, .spocially the 

@nraining allerbo! sbsdrE !, t!@is . sig!fi@l chill€nee in aymm.bic syn0!.sis. 

A wi.ly of EtuBl prod@! wilh signifi@t biologi.ll .ciiviti.s, seb a (.! 

ptrsnignirc, ph@.ine, (-leddhdc .d tlhoBitrlie ont i! thb mrif. Duing 

th€ pre$nl study, . chiFl nel@philic @lalyn rc Edhcsize d s@sdully .nd .ppli.d io 

s*6tc 4 alkdbon sta@goic 6t r by O,{C{yl re!8@t h 95% c.

SECTION A 

INTRODUCTION 

I 

I 

I 

I 

I 

I 

I 

FE t }Spe|li|a of fdv.1.6.!,dtad|otTm)qm qtpa 

I 

I 

I 

I 

I 

I 

I 

I 

I

2.0 INTRODUCTION 

z.l 

2.1.1 

Itrloduction of fuorpo.d cripu 

The Getru! tlnoqprro 

DE g.nB ri@rol. (1.) Mi6. b.loDsirs to fdily Mait!.@.., obpti$ ?5 

gcn@ wirh 520 speics lsiddiqi, M- A. et al,, 1914]. TirctPotu is d impoi.nt gds 

with abour 40 s!6i$, Mey of lh.e e widely cmployed medicinal pldts throudoul lhe 

ropicd a.d subtmpicd cgioG ofAAic4 Sorth-E€sl Asia and Au5talia h P.lisld, a 

mlur.l s!ci6 I tu/arqt a, .td a cultiEld spei6 I @r'/old c fou,ld PEvioG 

pnfo.h@ic.l sMics on i!rc @!stitu4$ of g.!s Ti6@/4 hwc Gsulted in ii. isl.lion 

oa . v&iely of compounds, ircluding fidno

ui!8 diffqd pans of Tin$poa oisp' in atwedic medicine tAltm.4 f. B. .!d 

Holdsord, D, K,, 20031, 

VdioE spei6 of ttMpo.d e ls€d in fEy vrlushlc drugF and cxlibi *v.d 

pbm@losi@l &ijvities, Ior .&mDle thcy e usd for the ftatnot s febritug., 

siau!o{, dafdia, clDf@ {d s a $h6ritut fc qlinie lsiddiq\ M. 4., et at-, 1974; 

Pdry, L- M., l9E0i Eabal M€diciE R.s.eh Cb'4.. 20021. 

2,t2. 

Ti@pqa cttpa (Fa.2.0) i. *idely u$d in Thailm4 Mtl.ysia dd Indocia for lhe 

tr!.El€nl of j.bdie, fiematis, Eiury dierdc6 sd inGron f.E. I nislt is 

also usd d a r.mcdy for disb.tca nellihs in Th.iland drd Malaysi4 b.eue of its dn 

htFlsly(:dic cfl..t ThG kxi@logidl srl|di6 u the cndc cn@E ot T. oispa lat. 

shoM ninimal .ff4ts [siddiqi, 

M. A., e, at, 1974i P.rry, L. M., 1980r Hdbal Medicin. 

R6tuch creup' 20021. Fouowing e srlidt mcdj.i.al ws of vdios lt@t@r4 

> Ti8poru Mloberica Mi.e it a nch eu@ ofalksloid5, Th. aq@N.xlra€r of th. 

plant b uied lo ftlr liEr ed .y. dl,ndt , whik it i5 .1$ ftnoB a a dsu. 

builda sd cmetic lFmsort\ 

N. R., 1988]. 

> Titwpotu coaifolld l\llu ) Mid bG ba us.d for 0& ltalncol of veioa 

ailnenls i. rrlrvedic pFp@tioa for ccntud$ such 

ss&Bs, impotcncy, viol 

'3 

heparilb, jedie, .@ndlry sphilie, rnd uinary died6 [singh, s. s-, €r al.. 

20031. 

Triditionrl cd ncdicimt u36 of sode plrnts of gerus 

t2

Ti6pda baeigi F@ has b@ u$d 6 4 4ti-mal{ial .!tt 6ti-Pyr.tic 

plet for a long lim€ in Th.iland [Manin, T. s., sr d/.. 195]. 

> zi@spqa snilrci@ Bcnt.. @lmo y tmh N $!rcvie',16 b@! N.d in. 

tadidoml Abotieinal m.dicires for thc r€otu€ ofa le@kably wid€ r&8. of 

disordcts [Bk*q N. G. ed Nwiq'! 1., 1983]. 

> r@potu tiftBis Qlv., Mi€F. is ktom for ils et -intla'malory, feh{itugtl, 

sti-pdiodic ad dli-b&t rial prepdlid [Bisl 

N, O, .d N*aiMa J., 1983]. 

> The bittd lub€rcu tua of nwporc tdgitld.loli!.\ ca$.p bw. lolg been 

u€d fq lhe tran&n of ough and oib{ thro{ .jlnots [Bisel, N. C dd 

NMi$tl, J., 19831. 

2-r.3 Tinawn c.isps (L.) Mie$. 

Chssificatiotr 

SubtirgdoDr T@hobiod&V@dr plsr.t 

S!p..divi.iotr: SFmatophyr! Sedpl&b 

Dlvbiou Magmliophtaa - Algiospqns 

Cb$: M.gnoliopsida - Di@iyledoos 

srh.Ls: RlMculidr. 

O.den R&uculal6 

ruit: MeisFDr.-€!. 

G.!u: ri,ospara (willd.) Hook. i & I1to6 

sp.chr: .,:'rd (L.) Mi6 

l3

synoly@f IrE &aptcd $i@tific w it TttdPqo atspa lL ) Mi6 witt .u|ffia 

srynyff: M^kP.mM qitt@ LiN., Mdbpcm iM@ Bl!@' T-t@tlna 

cordilolio F.-vitt.. Coeuhs Mdilotiu w.tP, Co'cul6 'Ilrot6 DC, Ti@tpom *ispd 

(L.) MieB, d H@k. i & Tho^s. Ti@tpotu tuber&lala, Ti4oiwa runphii, C@.t16 

oispw, M.ni:Wntn trb2ranatwu\d M. w@. 

artbo.ilt: (L.) Mi.a, q !i@1, t & Thoru. 

Atb . Tinospod .rtspz is 6 .linbing irc€ wilh ll€ms @hirg a hcight of +10 deleB 

Th€ sr.6 e u/o I dlibctd lbi.l ,nd eon v!,r fl6hy ltd pojels od aom iG 

slmddines, 'Ih. l€v6 c tlja .gg $4c4 Gl2 cdliD.llrs in ldelh ard ?n2 

endn.las in fidth, willt pointed od lcngthcn or sorewhat h€.n{h!Fn ba*, s@0r 

ed shining. The flow* @ p6le gen &d shon sialk The tlil h 7_8 hillim.les lon8 

lLbirttt Tin pala ililpa ftrJnd in hopic.l dd sbtopicd India atd Dsirs ofihe Fe E$t. 

ed in Fnary dinfo6|5 or nixed sbld.d fo6:ts 0@ug[oul dE PhiliPpic; in trepic'l 

A5i! ar oltiru.l€s !p !o 1,000 metes. ni! troPiel tree wilh shiny grcd l€af is also widely 

dbrribul€d in hdon€ia Mabrsi! (ed Bo!@), Th.ilold atd vicljm 

Oe!m..: Diiribut d nGdy in ftPicsl .!d $!-topicil Anicr, Sourh-&st Asia, IndG 

Molaysia ,nd Auslolia lsiddiqi , M. A,, .t al., 1974t Psrv, L M., 1980; H.rbal Medicinc 

R.s@h crcup.,20021. 

Oc.m.. in P.Lith: h P*isl,4 ! dfftl sPcci6 T-orPota didb4tru is foud in 

RavElpitrdi division .rd slduding !6, .long eitb a cultistcd spei6' rloM a 

La.l N.nB or r. .tit r. MataboDi (T.g-, Bis., IIL); Hindi: dia, flridbuti' Tmil: 

klrruttodi, T.lus!: chip@-tig.; &atrlcii, Mrhyalto: d!g.di, MGtbi: f&idbel; jmnk 

l4

.l. Ird@si!: bFtlvaq ed.{tli, putiqsli, d.u eade Thii:. boE!h.! qd knb hoi v.i' 

Mal.ysia.ktE p.tawali. 

2.1,4.1 

Etbtrobotrny of fitaryotd cr.il/d 

folllorc &d ar.dlrionrl u.. 

In Intlocia, ilE mlin poducls oft"diiioml ncdicim, callcd "jdu', onc 6on difieFnt 

pans oI mor thd l2O sFci6 .nd fi,trpofd d/iitPa (brotow.li) is o* of lhGE. An €$ni. 

gDup in Sa!.i &d the M@l comuiy i! Malatsia @ ?iMlota ./nPa b tEal 

di.b.tes. ht?.ndeo. dd lmbogo fAlmcd. F. B. ed Holdson!, D K,, 2003]- 

A &*d@ of dlc adtrt leve .d.@B ot TrbsPom ctitpt tre.d 10 n fd.r, 

'5 

.holeE, diah€tcs, .heumtbn dd sEl.-bi16, An iniaion of lhe slem is |ato 6 d 

v@itu8., whilc daetion of th. stem is u.d for wshing e.. .y.s dd svphrliilc ercs 

lsiddiqi, 

M. A., ., al., 19741. It at$ EdlB tltr6! inlqDal inltamElion .d incrtag O. 

appelite. The drug fron sten is cgisteEd in th€ Thailed Phmacopoeia !o t'tal diab€l.s 

(P.dy, L. M., 19E0; Edu€rdo, Q.. 19781. 

Ir goeral folUoG, the slem d@ctior of Z cf&p, is cosidcrcd etjpyeiic, dli_maldial 

&d s a ssh for ski. d6. TF4loially e itrfusi@ b wd !o ftlr fev.r de to Dalsi." 

j.udie dd lgairst int sti!.| soffi. TIF elinalairl .tret is ale cF tld [Rdn & N 

N. N, A., .t al., 1991. The cMhed l€v* of 11 crbpa e apPlied on woudds and m.de 

inb poultie tu 't!'ta [Umi Kde@ Y ard Nd. H,, 1995. 

Th. Fopl. of Philippines dd Malaysia coro'dd the sten of I ctop4 6 d sieesl 

nedicie. lt b mosl Fpuld 6ons all the l(.l n dicinal pldr.. Il ie omonlv 

pteibed for h. trErmat of slol@h t oublc, indig.stlor &d didho.a lt is al$ e 

.ff.ctive medy in the Ee.tedl of trDpical uh6. A pFp.htion in @onut oil is claim.d 

l5

to b. d cf&ctive c@ for rhdtilris aid {or fllhl6e ir childm [Uni K'lsn, Y dd 

Nmr,H.,19951. 

A .ldoction of thc &$h rcots, nixed with FpF ltd gosfs mill, is giv'n for 

rheBnlris, in . do* ofhalf! pint clery moDing [N.drdi, L M "d Ntdtdi, A K 

19991. It is als sed di€mally 6 a @ling and s@lhine applicsrion in ptuigo' e*m4 

i6Fri8o, clc- D4@ti@ of tt @is, in @obinali@ eith eirga.d $8d, n givo in 

@6 of biliow dysp.psa &.1 fcvc6 wiih oth.r bi!.F &d Nnarics R@Is rubb'd wirh 

bordF nuls in vlt r e siB i! !r.o.ch s.b., 6Fcidlv in c[ildd [Ndl@i' K M 

,nd Nrdkdi, A.K., | 991. 

Lt.12 

ridpord n,spa hs b€en !s.d fo! tlt€ tedncnt of d nMb€r of Phvsiological disdes 

Trbl+2,I I Mcdicinal tg of LdPota .fitla 

ar$-byp6glycr@ic efl6t 

ipFC-t'!ns 

lm@modulalory agdt 

anti{sdml Md lipophilic..tivity 

AnLin@'ceoriv. ud &ri.inn.@arorv 

N@,H.dd tubcrcn S.I.1998 .] 

EiF, s;d s*iR" Lind.. s.. l 

(m"r'hi!, N., er a/., 2002 

S'naidd, M. R., er al,,2008 l 

l6

2,2.0 secondaryMet bolites of Tinosporu oispa 

A nmbq of sondrry n.laboliles have bco isl.tcd lom vdios parts of li@pol4 

crispa- Cldodoc-tt?. fuamdit€tpqE ladon s' s di!@ grcup of t.4Emids wil! mod 

lhd 8OO looM @opoNds [S.l.tino, S., €t dt, 2002, is one of ih. host inponel d6s 

of l€rFeidr of ndp,tu. A[rloitts, ttmil55 di|rFe le1on6, Itilspqcs' 

equt€rFnc slyosidca, flavoooi&, ligls, phdolics dd mis*lldHus dass of 

6mpornd! h.v. afe ben ohain d fr@TituspqouaPa 

2,2.1 

Clerod.lclypo Fur.noditerp.mld! 

This is the mosl abdddt and int.Niv€ly invcstigatcd cls of F@ndarv Eebbolilcs' 

folrd in lidrota sp@id cl6.

t23 Prwios 8hdi.. or fir.?rt cd9. 

h ih. bd fttr a"irao., *tt.l r.c.d&y tattoub. b|v. hc.6 ided .!d 

.h....rlr.d nc lb.4t! d4t (TiA2r! Ib..oet D.rddn tddt ro 

diE cle ot dnl F!dd. Sd of b..c .@td hY! ba sld tu 

wi@ Uob€i..I drid., 'fiL t@. !d. t .r u.ql . dci6 fr. drbd 

d|6ctni..ry. 

IE

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3! 

---eil5 

30& Rr=o-ctro 

3l R=Rr= Ocll 

32 R= OCH! R'= OH 

; an* *-"-\"\ z\" 

*yr)(+r,* *,r\/ "Ar-.*\, 

n)\? rj 

a6 

( ( 

{0 (E) 

4l (4 R=H 

4r(4R=CHl 

39 

4o14 4r(r)R=H 

42(r)R=CH! 

22

lt 

1|'

5:l 

g 

24

-48 

r1l .b 

'i-{tr 

62 

63 

64 

ADrL.prr.(6-r)+Dslc.r". 

x 

1\ x I x 

25

23 Biogynth.ticPrthxay! 

> Iropre& R!1. rtrd T..!Eroid! 

Seondaly neubolites with i$prrc e thc b6ic uils md wiih m hpiical fmula 

(Cillji e boadly classificd 6 t rFnd or tdF@idg Moy natunt p@dwrs tub 6 

terFrcr steoids, ctc- @ e fod.d by difidt cmbimlion of iepEre uiis in he.d- 

T.rF@i& play a vital rcI. in thc lirs ofhmy orgaisG by cxertine hehbolic cont ol 

.d by m.diariq in int6- sld int r-!p.ci6 irardion!, such s poliDt@ ald d.fcG i, 

plets. Teipenoids re biosynthsized in i& difeMr pathwys, bded on th Min 

buildirg bl@ts, isp.nr.ryt diphosphar. Cpr) (sch€Dcz,t) &d din Oyt attyt 

diph6Dlt i t!. Dcrhyldrduirotphospba& (MEp) p{hwy or I n6xy-D-xytutc (DOX) 

?s 

26

Flhsy ir th. chloDpLst fo@ IPP for ooto- ed diGrpemrds, .nd ih. ncldotic &id 

OrvA) pd{rw.y in th€ cylosl, prdus I}P for sesquil€rpooid. Pu! A., .t 4/.,20011 

A-_^-\-\- 

E 

*.,1 

S.h@-2.r: Biost bsb ofr.rpcmids ir pt.&tr slowirg the maslodc &id (MVA) (A) 

dd lnoxy,Drrlul@ (DOX) (B) pothmys fo. rh. prcduclion of tpp. 

> Md.lo!.t Prthrry 

I 

""-l.z'." i.-; 

EI 

Th. qtac in pl€rts is oNat d io ..dyt{oA aad @nd65ed *ith mI[a uit of 

4.tyl-CoA 10 8.nerar€ a@toa.ctyl-CoA (Sch.m€-2.l). Th. addnion of. third ac4yl-CoA 

yiclds (,t!3,hyd.oxy-l-n.ibylstutdyt-CoA GrMccoA), *.rich is $t6.qEnily Gdu..d 

by dr. €.zyn HMc-CoA Eduq4sc io (n)-Devalonic acid (MvA) fDubey, v. S., ./ at., 

20031. MvA fien uodcrgG . ei6 of ptssdoryrarioG, tN of CO, ed imry&i. 

tl 

a-r^_i_ 

9" 

" ^..^"-l-; 

2l

ldro.luction 

> Mwdonirclld.pdddrPrftrly 

Thjs parhwy w6 di*ordd in aly 1990'r $rcud meh on sve6l belerial strains 

IRohnd, M., a ar, 1991. MvA-indelcnd.nt prlhsy b.8iB wnn rlc @n@ion of 

glu.4 itr1o Slyce..ldcby.L-3-phcphlte (CAP) dd p,ruv.le, foUoved by {idi*, 

medial.d d€c&boxyl.tion of plnvat, CondeNtion wiih CAP g*BLs l-doxy-D- 

xylllo*s-phosphnlc (OXP), D)(P rhcn und.reo6 ! l@&gendt dd educlion lo yi€ld 

2'c'h.thy'-D

T 

I 

(3P4 c"i 

I 

l'+P4 

I 

l-- 

]_".*"' 

Ak kk-i4PtE rdcdFets 

Fb. 2.r: Srrth6i! of veioN ctNs of ospetui& in !tdr!. 

Prayld.d Feia tuoid3 

Tlc noFMVA paihwry iB widely fibc[olal i! €uba.i.ri.! ad ptoG lRohnd. M., t999]. 

In plals botl pst[Mts ol]a opasr! simut Musly. TtE MVA pd[qy nlEtio6 in th€ 

c)loplsm and b GspoEiblc fo. thc.vdrul pmdEri@ ofihe slaots 

"rd *"Cuir.rp*, 

(Schcme-2,2), ehile rhc ioFMVA parhwy iniriar.s rh. ptuducton of clrorcn s, mom_ 

arn dnaFm3 h lhe cbloo9ksas (fig. 2. | ) {rd dF lbiquim sid. chain in mn@hon&i. 

29

Intrcdu.tio, Ti,osporu *itpa 

lM. S.hsra M. ad Arisoni, L D., 1991. Codins of llP ard DMAP @y l.id ro rh. 

dif.Hl cla$ of lerFr.s, 6 shou h Fig, 2.1 , 

2.3.1 Bi6ynth$is of Clemdarc-type Furaroditcrpenoids 

Mainly ctr-clmdd€s have b€o islal.d lon I .firp,, althoud both .ir ,rd tca 

i$ncE @u .bmdully in n!re. h hq bd disv€Ed th!1 i! cLed6c-1t?€ 

ituodilerp.nc lelo6, C-1. C-2, C-3, C4 and C-6 hav. bea rhe mosl erive sitcs for 

oxid,rrio .poidarion &d h.toizatid Ir gtrrdl biGrdb€ric Ftbwy 

typc fui&odilcrpoes is shoM in !ohcndz,3, 

for cl@ddc- 

It ha ba prcld U.r C-2 of MVA eiv. ris ro C,l, C-7, C-t2, dd C-18 of dir€rFF, 

whil. C-3, C-5, C-9 sd C-14 di* frbo C-3 ofMVA lrd C-2, C{, C-t I ar|d Ct5 lion 

cJ ofMvA [Aknib A., a al., l9l]. 

c&alebdac is fomcd fbd ccPP Oq yr4 rm ditr@ni reues. fi-na76)19 ltunk 

A, Schem-2,2) ed 76r81J82+83 (reuro B, Schem.-2.2). Sihildty, th. biosynrhesis 

or ,ra6{Lrode follo*s eilhd reuG A (?6-z-7EeE0, Scttu€-2.2) or reu. B 

(76rErr82r&1, Scbcn+2.3) 

In cyclt lion of 76, rwo intemcdid€s ?7, El w.rc prcposd. Ir @ prcde €ither q_ 

n thyl al C'lo dd FH .l C-J (763t7) d cyctiz.rior nom 7cJ8l vill Fod@ &.ncthrt 

al C.lo dd d-H at C-5 d.p6ding upon lhe.lrack ofrhc doubl€ bond (C-tO/C_l D ai C.6 

of OGPP (76). Funtq l.smgd@t by l '2-hydrega siin fron C-9 to C.8, t2_crhyl 

shin froD C-10 b C-9, dd l,2-hydrcso shift tun CJ 10 Cno in ?? ed El,led !o 

intcmcdiar€r 7E &d a2, Esperircly [Arnib A,, .r dl! l99t; Birch, A. J., a al, 19591. 

30

A c'19 mehyl sltift to C-5 in ?E (roub !) od in E2 (oute a, ptudes r/4ro{lcbdue 

skelclon ?9 {d 84,6!@livcly' *d.t6 ! C'l8 bdltvl3hic to C'5 in t8 (re e b) cnd82 

GolE b,) produ clt{lerodde sk lelon 80 and 83, Gpdtivelv (Schdc-2.3). 

db,dh!$,hM-,t 

0e) 

(? 

i$\ 

(16) 

Sch.nctS: Biosynthdh ol olercdoc-trp! dit a€noi&. 

(El) 

l

Intrcductioh 

2.32 Bidynrh6is of Aporphift !d Tyrrnioe Alhloid! 

TituWra 'nsPa 

An dim &i4 9rcsinc, is the min $uM of benztlislqrinolire dd tttdift .lkdoids, 

rhougl mdy dtemdre p6th$ys harc al$ bca popos€d for dre sFlh'sis or 

aporyhinc ed qrdinc dlaloids h natut [F4bini, 

P. .t and Biid, D. A' !98]. L- 

lyrosi@ (87) ir th. pt*@ of L-tysit JDOPA derboxvle GYDC) C Ed@d to 

t'I@iE (88). oxidatior or tlMift produB ,LhydsxtThdyle€bld€hvd€ (E9) which 

th€n @nbin.s wirh doPdine (E6) (eob Ldop. r) io F|odw (Slnot@laui* ($) $at 

.vsnlu:lly le!d5 10 difffil t}!es of b.nztliequinolin€ alktloids (Schehe2 a) 

Monovcr, lyluift (t8), in.ombimtiotr *ith @umyl-CoA or f.rulovl4oA, podrcs 

hydmxycituoylBrmims (91) dd Flai.d uid* (fth.ne2.4). 

{35) 

(36) 

4.Hydrdy!h.nyl,c.rd&htd. 

*-el^* 

I '"' 

raY'r 

(33) 

rd 

S.he!t2,{: Bidydhcsis of atoehlnc md ryruire nbbids, 

I ('o) 

I 

[.'t'tr,qrfu|h.^]ldoid! 

tlydloryd!uoylrinb6 

32

CHAPTER.3 

R.ESUIL]IS 

AND 

DISCUSSION

3.1.0 

3,1.1 

RESULTS AI\'D DISCTJSSION 

Clerod.ft -type FwoDoditfr peaoid. ft on Tino sPo rt ctispd 

Duif,g the pscnt ph}tohmical iN6tig.rio. on the ncthNlic dE&t of th. &rial pans 

of Ti@tporc ctispd M6l^ysie odsln), 6n4i cldo

Nays were also pdfom.d on najd coinnucnts of ritdrtotz tnpa duing lhh snldv 

> G.rcr.l Stdctlnl Falns olcLtud..etvpc Frmodit'rP'noidt 

Cleod&crrF tunroditerF oid! Gpl€sl ! fdou cls of orgsic 'onpouds Thev 

€xnibn .h4acrerislic sFclal fdlG (Ms, W, R, 'H' tld 'rc'NMR) 

. M.s FdgE.!!.ii@ Pfth 

In EI-MS of clddd.-t !e nrr! odileDdoi&, ceialn tagmetrl ions Prcdodnaie 

*nich @ be 

ln this 

dN of comF6& rhe pl€se@ of n@ mi.ly is infdtd tlrougl lhe peM of a 

rnsmenr ion ar /z 8l (liagment ion 'a ) which diss s a Esull of bond fision .r c_ 

I r/C- 12. The cl6v.a. of C-9/Cn I bod led !o fsgnor ioN b' ord c' whrc[ lplco al 

,1/z 94 aad 95 in the EI-MS sFct!. of fr@noditerperci rcsp€cliv€lv The 

Deiloxydbonyl sr c4 givc ih. fragD€dt i@ !t ,'/z 59 (d) (Fis 3 1) 

csHro' 

,t-R 

() 

Y 

.) 

corko- 

o) 

Fi& 3,1. Ch@re.icic tlB fr.g@15 of cledde-q?. nnlmdiLrP€rcid.. 

. Infirred 0R) .trd Ultnviolet (It9 Spet osopy 

Itc IR spetla (K3.) afrords strd.linc filqll@ie for GH (3551-3390 6'), c{ 

0?45.r550 cmn), tuM rins (1504-143s cni) dd c-o.c 0090, l0l7-l04o,lol5 cmr). 

Th. Uv spetra aully shoq (l)E lb€olplior b.nds in ltE dgc of 225-200 tD 

(d)

. 'H- rd rrc.NMR SpeiM@py 

TIE rH- ard rt-NMR lpeh ot .Lrcddco?. fimDd;ierp..oidi show lhe Fega ol 

re egule methyl srouF, M€-19 (ru LoGl.66/4 19.+29.7) ard M.-20 (r{ 0-81_1.15/r. 

23.].29.9), a 61et n thoxy (rr 3.?5.3.8?/rc 52.2-53.4), two €std cdnonvl (dc l?12_ 

180.5 ad 16?-6 175.2), &d a rl&to* (C4lCi or c4C-8) or 6_l&toE (c_8/c_12) 

'Dr ptts€@ ofa n@ rins i5 $pFrt d by lhc sigMls d & 125 8-125.E (C-13); 109 4' 

109.9 (dH 6.5G6.55, Gl4); l,!4.?-145.0 (rH 7.48-7.50, cl5) ed l4l ln4l-6 (& ? 58' 

7.60, C-lO. Irr s|c@chcmist y of D-glu@pytuosyl is deLrhincd on the b6is of 

@uplins @sla"t (4 fm thc mmic pblon ofl-tlglMpt@syl ("E 6 l _?.7 Hz, H_ | ). 

Thc tB-dngjucdon in @bpounds l-15 ws d.dued !o b. cis on rh. bsis of 'rC-NMR 

chcmicai shltu of Mcn9, which s@ found in lhe dlg. of J 194'29 ? qhile in ta6 

diiposnion. oEy a!F! bclwer d 1l-19 [Mmb€, s. &d Nishitro, C., 1986] Il)e ting 

tusion b.teq Bi/c dn8 B d\ttemiftd d lh. bsis ofrrC-NMR chdical sbitu of C_ l I 

(< 0 45.0 for ci-tu!.d riiss rnd > 615 0 for ta'r-tu$d tilgs) Ktt4,M. A,et ol , t9E9l 

3.l.l.l 

3.t.l.l.l 

New CoNtitu€Dts 

Rlopbiol E(l) 

IUPAC: Merhyl (2x,7t8s).8-[(2$2.(3,4-dihydrcxy-2,5{im.thoxycrr!hydrG]-fu@yl)_ 

2.hydbxy€thyll-2,8{imedyl- lo{K- l l -oxa|JicyclolT.2.l -02rltlod*-34n€'3-@boxylale 

Dri.d .d elourd did Frls of linotpoo ctispi (16 Kd w cxi.!.Ld wit[ ftrbed 

ed panito!.d by $lMrslvat extredon into fou min dE&G (Expcrincdal, 

&dion-3-2.3.3.1, Pag.'ll2). Conpoud r (1.2 x l0'% yi€ld) w6 obiained s a while 

elid fron the .tnyl elaL dtEl {69.43 d by sesiv. @lum chmbalosnphy on

CoDpound I ha rhe dol@ule fomuro ClHr.Oo s d.dw€d fiob HRES!_MS (+re) (M 

+ Hl' ^ D,/z 4n1.23r2 (cztcd 411.2225) (Sche6.l.l, Pasc-ao. 

Th. EI-MS,IR ard ljv sperE show.d chr&i.dnic fatuF of 

d.rd,ctyF fi@oditerDei6 (Fig. 3.1, P.g.-14). Tle 'H- 

NMR spocEd of r Gablc3.l, P.sc-41) slo*td sigMls .l , 

4.23 OE, b$, s-14), 4.9 01I,4 4.{ &= 2.? Hz, H-15) .!d 

4.90 (1r{, s. E-16), dsisDed 1o Ltdydrctunn noicty. The lH- 

NMR st6rm ,1$ dlibil€d a rclaliv.ly doM6.ld oxymedine 

lisnal ar ,H s-57 (bid. F 6.0 Ha H-6) 8rd a El.tjvely lpfield 

:( \/n 

oxym.thinc sie!.I at ,H 3.84 (d, F 7.5 Hz, H- | 2). Ttr methyl si8tuls at , l.l2 (s, M.l9) 

!d l.16 (r M.-20) w@ dE ro &sdr n4hyl gouF !t C-5 ed c-9, dFcnvcly. lt 

fidhcr sho$d t@ n lhoxy pretor silgLB .1 ,s 3.47 &d l.4l . 

Th. BB (hosd&nd d.couplcd) DEPI uC-NMR !!.e'u (Lblel-|, Pasc4D slo*td 

siSn ls fo. 23 cirhoc, irctlding t*o nc0tll, fivc D€Oyloe, six Edtift, fre qualqna.y, 

rhp n thoxy ed tM 6&r dbdyl. T!. wbooyl caftoN at, 180.5 ed 156.? \l@ 

.isig!.d to C-17 l&lorc and c-l8 m€fioxy 6td. Ts manoxy sigtrds at , 56,4 dd 54,8 

l@ tue ro C-]5 dd Cn6 meilbxy grcupr, sp..livcly, The sielal al , 5l .6 wd du€ lo 

c$.! melloxy aI Cl8. Two ncihyl 

signals rl ,2?.0 ed 19.9 wft dE 10 

&Sd& nctbyls at C-5 dd C-9, 

Gpedrely. Ile doqfcld sigirk d 

6 69.0, t2.o,762, lll.7, strd 109,5 

qe Nign€d to C-12, C-13, C-14 G 

l5 ed Cl6, EsrElirely.

T1€ 1H-rH cosY sp€IrM of lh€ @npound r cie. 3.2, Page36) snored viciml 

@u!lin8s ofc-l protoG (, l.% ed r-q) with C-2 (r 2.40 ard 2.30) ed C-10 (d l.4l) 

prcton6, The olcfi c prcron (H-3) showed cressFils with C-2 methyLne protons .l d 

2.40 (H-2a) dd 2.30 (H-2b). Sisrals d 6s 2.n Ql-Ta) dld 412.11 Qr-7b) sbo*ld vicin l 

colplings with C-6 (d 5.s?) &d C{ (rH 2.43) d€lhift poto6. IlrlhmoE. @uplings 

wrc ob6eNed b.twn the poto6 al& 1.69 @nla), 1.56 (H-llb) and rhc nethine 

sisdl .l r{ 1.84 (H-12). TLc crcs-pel b.t$€o rr 4.21 and 4.97 wa atr.ibutd ro 

couplinS b€treen Hn4 dd H'l5 of6. &trabydrctnd ring. At thh poirl, two fralrn.hts 

A ed B q@ d.dm.d (t6endb A ed B). 

'Ir'e ftagnem A &d B \|@ join d toeethd od 

ihc b8is of hct@oeld nulriplc bond 

@fthiion spectro$opy (tlMBC) (S€e slors.!y). 

'ftn is d inlte NMR lehniqw uscd to d.d@ 

the long-@ge hci.onel€d inleretioD. TIE 

HMBC sperM showd frseFdr (Fig. 3.2, Pa8Fl6) b.twr H-6 (4 5.54, H-? (dts 

2.27 $d 2.18, Nd H-8 (6A 2.41) wilh c'l ? (& 180.5, C=O), indi@ijn8 th. pEen@ of o 

It&ion nnctionality betwn C{ &d C-8. The pI€sM of a r-leton rins w6 als 

supponcd by a Eldively do*nli.ld chdic.l shift ofth. C-17 ladon carbonyl (,180.5) 

due to g@l€r nng st din [Pavia, D. L., .r al., 1979]. O.c@nce of ielElydrcfur& 

nrcdoo.lity B infmd nob th. sisnab d, E2-0, 76.2, ltl.? md 109.5, stich wrc 

atlribui.d to the foor oxygdal€d cdb@s of C- 13, C-l4, C- 15 ed Cl6, asp€.tvely, Th. 

lons-@8. r.I @rclarions betwdn I{-12 (rr 3.E4) and C-9 (dc a9.D rd C-ll (rc 82.0), 

along wirh its COSY @ftlatiotrs with tI. C'll methylenc prclons (dtr 1.69 ed 1.59), 

indiet d the teo.dbon chain linled h.iw..n nlg B ed the t€I6hydrcfilm nohry- 

Bascd on od!€d$i *ith lhe data of tLe k&m 6npo6.b lMartitr, T. S., €r ar, 19961, n

s d.dE d rt r c.l3 (& 82.0) 5nd C-lt (4 ?5:) vq! bldroxtld.

'rni. cLs of .@Flrdt i! lnovd 6r cyt Ltdc divili6 .g.i.d hlD. dd .ptll.fud' 

f.d'ilr ldd c.l@ c.e ..ll li!€ [Sh.., X C., .r. d, 20051. Clqld@ttpe 

nJI@diFDls blE .bo Som irst &d$cdtd sdvity rcinE c,D. L,.L d ,2w21 

I 

I I 

Cit 

s.h.nr3.0! Eiogoaic relt i! t}!lh6i! ofclcmde diLrpdt & 

39

tr'\ 

) 

c6Hi 

-8 

)a 

coHto" 

r|.. 3.4! PdpariE NoBsY iffiim h l. 

cuH,3oi cdrrros 

t63 

;l 

cllHlJor' 

x 

clHror' 

ir'zt E5 l\oe/") 

5i 

csHso* 

a 

S.h.oro.l: Ma Argndrarior prtt m of ompourd L 

csHTo+

T.U;3.r: rt'- |!d |H-NMR'chdicd rlifr d,i! of @Frod ri , i! PPo &d J in Hz 

c{ 

ot2 

oll 

c-lt 

icnt 

c-t9 

t6J l.e6(GbI r.e.(wb) 

r3l.t 

tt.9' 

CH 

CH 

ctl 

cx t..1 dd (4r 'r t+ JL h- 1l) 

39,7 l,6e dd (.r,. rr' l5J.4r d xt} l5 (oiit|.p 

lllJ 

21p 

CH 

c 

CH 

c 

c 

'Sisndr e id.db.n8!.tt . 

rR@rd.d d?5 MIIZ in cDctr. 

'R4dd!d .r 300 MrL in CDClr.

!.1.1.12 2-lydnryhonP.i@l& c (2) 

IUPACT (21,5i,6i,Ei,9s,10s,12,5)'l5,lcEFxy-2'hydrqvq4D.glupv'@svl> 

cl.od.-l,l3( l6),1+t!i6-l7,l2.li.l-l E{i. rid E lhyl6i6 

A ruFt&dd Fb3l (2.1 s) nm tl. bul&olic 

dt?ct (?2.61) a dbsolrd in ft.lhaFl to 

tEmv. D.ihel iMloblc cdFdrb ud 

tiltr.lion- Flnhd puif@liou of tlE tldl|@l 

$hblc fr..tion by 6ine Eyclilg HPIC (GS-320, 

l0 M.OH) yicldc 

irA 

2 

x..1,] 

TIE ml@ll fdnuhof mpouDd 2 s dcdlc.d c CrHxoron lhc b..! of IM 

+ Hf 

ar al 553.22t5 (6lcd 553.?2E0) i! HRESI-MS (+E). Tbc EIMS 3horEd cb.Fcnsdc 

tugndrnid of cl.redet F tuD.ditaPad Gis. 3.1, P!8d14, Scboe3.2, P.8e 

46). TL Uv lpoctu showld.teDlio! b.!ds at22l, 217, 201 M. TIE IR sp.c!@ 

(KBr) lhow.d 3lr.r.hilg b.!d! fd CH G409 cEn), C{ 0709, !670 mi),.tontdc d.g 

050+143E 6i), ad c.o4 007E, rorT cD ) n!f,dooliri.3. 

Th. 'H-NMR sFcEM of@pourd , (I.Ue3.2, P.gca7) dbPLtld tilc ringld!, och 

ilt4tFli'g fd lhc p'otoE, sig!.d to Mcl9 (rH l.5s), Mc20 (rn 1.09) &d c-18 6lcr 

mthoxy (rx 3.7t). Tbc |H-NMR rFctu.!.o $o'rd 0r oxygdttd ot i[iF lisdt 

.r , a.49 (rd, Jr. l= 8-3 H4 Jr j= 3.8 H1H-2),1.53 (d, 4f 4.6 Hz, H{) .d 5.77 Otd, 

4:c r r= t2.4 Hz, H- 12). sisltb fd c-3 olcfilic prolor lppotEd a a doubl€l .l , 6.59 (4. 

r= 1.8 Uz). A doubL doubla ll , 2.13 (Jr tu- 6.5 Hz, 4. rr= 

| -5 Hz) s sisn.d lo {E C_ 

E DdllE Fotor Thc c.lo oElhiF Ford.ppaEd ll , 2.55 Ord, io r' 6.0 Hz, H-10)

SiSn.ls at d 2,20 (dd,.4lArh= 14.6 Hz, J412;' 12 4 Hz,H-lra) &d 1.67 (dd' 4rqrr0= 

14.6 Hz, Jrq u'= 1.5 tlz H-llb) *rc 4sigmd io $e Cn I n€lhylede prcloro, vicin llv 

@uplcd wiln th€ c-12 oeihin 

troton. Th. plE$e of a nlfu 

ling 96 inGFd Aon 6. 

chdlcrc.igic signals al ,H 6.53 

(hs, tI-14), 7.48 (d4 45. l- l-5 

Hz,lJ.s= 1.0 Ha H-I5) and 7.60 

1.65 

6.51 

2.m E 

J". 

(bB, H-16). fte mdliplers at J 2.25 (H-la), 2.00 (H'lb) ed 3.20 (H_3) qee ale 

obwcd. The sign ls al,4.41 (d,J|a1!= ?,5 Hz, H-l').3 l7 (d4 J1r,i- 15 Hz, J,^Ji= 

7.9 H1 H-2'), 3.39 (di J1r,ta= 9.4 Hz, J.tlF 9,2llz A4\. 3.80 (dd, J6t 61= I 1.9 H4 

J6( &= 2.5 Ha H{h) od l.?0 (d4 J5!6n= I | .9 Ha J6a ft= 3.9 Ha n-6'b) wE NigDd 

ro ploioG ofp-Fgly@ptm6yl o@ity, subdrrur.d !t C{ of cldod@_9?. skderon 

Th. r3c-NMR spemm (ra!le1.2, PagG4?) of@mFurd 2 iDdic.r€d th. plls.M of2? 

@bo6, ieluding ore nethoxy, trc pndsty, fou !@nddy, fouter lerlidv, dd 3ix 

qurhary cdho6. Among th€n, two wft qut hrry.dho$ t 6 1717 (C)7) ed 

169.1 (c-18), eighl methins st d 64.9 (C'2), 78.4 (C-6), 71.3 (c_12), 105 8 (c_l), 75 4 

(c-2).78.0 (C-3),70.6 (c-4'),7?.2 (cJ ). on. nehylene ar,623 (c{'), d csro 

n tlbxy oi , 52,4, md olefnic nclhiE C- 15 lrd C-16 ar , 1,14,7 ed 141-3, rcsp..livclv. 

Thc 'H-'H COSY sFcEu of thc @mpoord 2 (Fi8. 3.5, Pa€e-44) €xlibit€d gcdin l 

@uplinss bct9d lte Cl trEllyl@ po&,s.r d{ 2.25 (tl-|.) .td 2.00 Gl_lb), vici!.lly 

coupled with clo (rH 2.5O a.d C-2 @0uft FoIos (& 439). Ille laltd showd 

corclarion wnh rhe c-3 c.rnitul n 1hitu sigril sl & 6.59. The @uplirgs of $€ C'? 

m€thylcnc poloB ar &2-67 Gr-?a) a4d 1.73 (H-7b) with H-6 (dH4.53) md H-8 (d{ 2.33) 

suppon d lhe @decuviiy ol C-6 to C-8, Th. C- l I medylene prctoN al ,H 2,20 (H- l lt), 

43

1.65 (H-l lb) sho*.d CosY creePct}l w h tlD C-12 Poton 

(,{ 5.?7). ThG cms'p€at( 

heiw€er n-14 (dH 6.53) sd H-15 (7.48) offud tins *.rc als obwcd in'ErH cosY 

sFclrM of conpoud 2, At this point f6gm.ni A w6 (ledued along wiln alditional 

sisnal tor oxygen-beding malhin . TlE rH.6d rrc-NMR dda, olong wilh cosY md 

HMBC corelatiotu, sugA.st d eoild fagnot C (P.8._43) and a 6_letone ring in 2 

n& t5: K.y COSY @frlai* in I 

In the HMBC spetflm (Fi& 3.6, P.8ea5), t* nlin @lariotu wrc obs td ttrqcn 

lle c-2 ca6on (rc 64.9) &d C-l malryL@ Foiod 

(& , 2 25, 2.00), c'l oLndc mcrbin€ 

pbtor (& 6.59), ed c-lo Gtbinc preton (rH 2 33) Sidldlv thc sldhoxvl Ptu1otu al,! 

3.?5 shorcd @ftlaliotu *ilh th. qul. siy wbo6 at rc 139-7 (C_4), 42-0 (C-5), 169 I 

(c'18) dd with rhe ole6nic dbon at ,. l4l .? (c.3). 'fte he$irc ig!.ls !t & 4 51 (H_6) 

sho*ed cof.latioN wirh c-5, c-6, c-? ud c-10 (dc 42,0, 7a4,29.1 and 42.0 

€sporively). It€s @relatiots suPponld ihc pGsa.. of a hvdbxvl (oH) al C_2, a 

rrisubstitlted doublc bond h.twen C-3lC-4, dd d 6tcr cehonyl ai C4. K.v struclual 

infomaiion q@ ohancd fton th€ @oplings b€t*d th. mondic Prolon 

at rH 4 41 (H_ 

l') with the c-6 (rc 78.4), od h.lhin Fltotu tl dH 2.33 (H-8) wirh c{, c_?, C_9 md c- 

l7

ll, C-14 cl6 dd C-l? (r. 1269. 109 5, l4l-l tld u?-2, cpetiElv). Ar lhn nage n 

@ etablished tlrar c@poud 2 bld ! clcode-D?c llErodic.Frc h.tom skeltuA 6 

Ttle NOESY sperrM of 

@npoud 2 (Fi8. 3.7) sho*cd 

cbs-Falc b€tsd H-ZMe- 

20, H-8,/}l.-20, H-12lH-10, H- 

l0 1,1el9 od H-6,4t-10. Tnis 

indic.ied rbat E-2, Me20 ,nd 

H-8 e all on ore side of 

nole'nd pbtrc {/), eltil€ H{, 

H-10, tl-12 sd M+19 e on 

rhe odH si.le (a) or lh. 

FL. lt. K.y HMBC coftlatios in r- 

nold'rle. The st wor of contound 2 eu d.d$ d, !s shos i. Fig 3.6 lX. *w 

@mpoud M sivd dE lm. @X.5l,6rl,8X.9S,tos,l2t'15,16

f 

+ 

I 

t 

ri \\ 

Sc!@e3} MN tugncltitio! pslt h in ohpound 2,

T.b163.2. ric -.nd TH.NMR'ch.cic|l lliftdnt of c@loud 2;, in pptn &.|Ji! Hz 

CJ 

CH 

139,7 c 

c 

159 

CH 

'H-nrm(r) l 

2:t (mr. 2.00 (h) l 

2r7 d'ld(4r*- l{0,rh. t.5,4rf.l I 

l,t3 dd (Jrr. lar,-h r- 61) 

ctl 233 d'! ({ r- 6J, Jrf ll) 

ctl 

CH 

CH 

c-t7 tn2 c 

c 

n2 CH 

-R@d.d d | 00 MHz i! CDTOD. 

heood.d .l 5m MIL i! CDjoD 

2:0 dd g|lr n.- r.,6, J,,. 'r- r2..), 

lJt dd (4'r nr- 1,r,6, J' 

't 'r- L5) 

ot 

clt 7I.ldg'1!-1,r,4'.1.0) i 

3.t ? da (4r 'r- 7.r, J:r n- ?., 

3-9 'l,lg.t^- 9t,J\h- 921 

3.tod(J(t' ll,9,J.\n-2.5), 3.m

3.1.1.1, 

IUPAC: (2r,5r,6X,8S,9S,1 OS, 12.'). I 5, I GEpoxy-2-hydroxy{-{l_D_gl@pyMosvl' 

(136)-a-D-xrlopyrooe]-cl€rcd,13(l6),14-i.icD-l?,12- olid-18_oic &id ncihvl 4tcr 

Th. sub-fE ion Mr (781 n& 5% M.OH in 

CHCIj) *a nM!6 pum€d by @ycling 

HPLC (L-80, $l.r-net@l l:l) to obEin 

onpoud 3 (2.? ds, l.? x l0_?o l.ld) 6 a 

colorlBs gl|my slid (Expdin€nid, senon- 

I2.3.3,1,Pagc-ll4). 

The HRESI-MS (+v.) slDvrd tb€ [M + H]r.t r/r 665.2701, @Gspondi4 io th. fomula 

CrHro6 (calcd 685.2708). Ile EI-MS of @Fpoud 3 ch@craieic tuSmcndon 

panm for clc&d@trTe fu@odit rp@ils (Fi& 3.1, Pag!-14) The UV sd lR sF.tla of 

@hpood ! q@ ld8cly sibil& ro @mpourd 2, lugg.dirg sinild tuncliontiri.s 

nE |H-NMR s?edu Gabte33, rage52) of coDpoud 3 drsday€d sigtds for lwo 

ne$yl, orc nelhoxy, ad tum nng proloD, che&i.risiL of clftdd6tvpc 

tumodircD.niods (Pair.'34). Th. 'H-NMR sPetuo ale exhibit€d signak for thE 

oxyg.d.d n.thrncs ar , 4-5 r (td, J\ - 8.3 Ha Jzf 3.1 E ;H-2),4.57 (btd, J6.f 3 0 HL 

It{) &d 5.53 (dd, JD4 u!- 6-0 rL,4,( h= 5 2 Hz, Hl2) nE sigDl.1d 640 (Jr.,= l7 

Hz, H-l) wa sign€

cgion of ihe speE@ at d 2.29 (H- la), 1.9 (H-l b), 3 37 (H-3), 3 39 (H4), 3.44 (HJ), 

3.31 (H-l), 3.45 (H-4), ard 1.52 (ll-59. 

a. 

'ft. discleid€ miety, AD-sl@plmolyl-(lr5>a-D_xylopvmo*, E idstiEed bv 

iB! diff.tun ds of sigldr Th. fr* !a .1 , 4.42 (d. lb 2r= 7 1 lU E l), 3.n

al rc 140.7 ws due ro c-3 ol.finic 

cirhon. The oxy8.n-b..ring tqliary 

carbos .ppered 61 6 64-6 (c-2), 

80.8 (C-6),7r.9 (C-r2), ?5.5 (C-2), 

?8.1(C-l),7r.2 (C4), ?6.5 (C-5). 

15.6 (C-2"), 14.0 (C-3) ad ?1.6 

Eenatins at , 106.3 sd 100.8, wre Nign d io C{'(GIc.) ed c-1" (Xyl.), rcsP€cdvelv. 

Th. doMfdd sniR ot ihc oxrtuthyl* @bon of B-tlSlyopytuosyl 

to the .oM4tivily ofc-6' vih C- 1", ttril. c"5" oxybelhylene app€@d at d 63 I 

.1 , 67 ? v6 du€ 

In rlF 'H-rH cosY sD@lrm of cmloud 3 (Fig. 3.8), ttc Cl nelh/@ Prel6 (r! 

2.29, 1.99) wd viciMlly .oupled *il[ rhe cno relhie (dH 3 45) dd c-2 @binol (4r 

4.51) pretoB. Th. hi.r sldwed . ftss-F3l *ii[ C-3 olcfbic proton (rs 6.40). Thc c-7 

nelhylene prcros (dH 2.2?, l.a?) shoqed vi.insl @uptinss wftn 1h€ c_6 (dH 4 51) ed c.8 

(rH 2.13) nethim ploroG. Th. Gll m.lhyLrc pretoG (ft 2.00,201) ed t. C'12 

nethinc proion (dh 5.53) mel.r.d wilh eeh othd. Th. c$s-Far betltq H-14 (rH 

6.51) ed H- | 5 (, ?.48) of s ntu ring vs .l$ ob&n€d. olr the b6is of EI_MS, HRESI 

Ms. lR, uv 'H, TTC.NMR ed COSY sp@tat d.ta, thd f€gndi5 A, B md c wft 

d.d!.!d s shoM a on page49. 

Tl€ HMBC s!@tun (Fi8. 3.9, ?.se5l) of conpoud 3 m id. ical Io obpoud 2, 

qcel for adaidonal orlaliou of th. Cl" dondic prclon (d 4.?8, H-1") ol 

xylopt'ee aith thc C-6 oxyncthyl€ne @bon of glucoptmsyl (d 67.7). At tIB stag€ 

it m clcd tha @mpound 3 had clercds€rr!. nmodil.rFne lactorc, 6 shoM in Fig. 

3.9. 

50

Ir dE NOESY sp.drum (Fis. 3.1.0), cDs-p.tb wE ob€w.d betwd H-2lMc20 H_ 

l2lH-10, H-81/Met 9, n-lo/Mcl9 .nd [I6IH{0, lllich $ggd.d l[e ridllIid of H-2, 

Mr20 &d n@ nne 6 9, ed that of H-6, H-8, tl-10, H-12 ed Mcn9 d c Th€ 

3i.l4h.nistry of DxyloPrd@ s 6si8n d ba!.d on the @upling oNlanls (, of 

almdc probn (1.,F 3.6ltz). On tbc basi. of tle dala lhc arnrtw of @mpoutd 3 

dcduced 6 @r,5t,6R.8s,9.t,10s,12+l5,l6.poxv-2-hvdbtv'6_{l-D_ 

slrpyd6/{l --6}a-D-xylopytuF}dc6d!-3,11( l6),l4rtr*l?,12{lid-l E{ic 

"tv 

FtrF r.9: (.y HMBC cmllri@ tlM h Flr*dw 

'"\ 

dmqing oromFu|d 3- 

o{4DC'r6otrrari113}zoryld} 

fl& 3.1.0: Kcy NOESY int.di@ ir @mpound 3. 

SI

T.brF3-3: '3C- &d 'H-NMR'ch@i.d sbin &n of mDound 3; , i! PPD !Dd., i! Hz 

c-t4 

c.20 

'R.curLd 

13J 

CH 

CH 

CH 

CH 

7t.l CH 

CH 

CH 

.t l25 MHz ir CDOD, 

h4ddld a.5m MHz io CDTOD. 

i:-(oEl'ellt{o€Lp, 

217 (oEl4 ), 1,47 I (4q D- 

I t r) 

2r, ( @Lp),2.01 (oELp) 

,J! dd qrL l'- 64 JL 'E- J:) 

r.8tdd(-/4n r r.3, Jq r- t,,3.67 &r g.r.-

3.l.l.r,a TitrNitp6id. B (l) 

IUPAC: (5r,6&8s,9&10l,12.!).l5,lcEpoxy-2{xo4(F}gl@ptt'syl}clmda- 

l,t l(16),14-ai4- l ?,12-olidl8-oic @id n thyl cst4 

A t!.tio! Fr63-2 fbn tLe b .mlic q!&r B nrrha 

hedooaied into thE suLnactioN (Fqla Fry-2b ald 

FrF3c) on Dolrmi& Bin by Glunon qith chloofod- 

m€$mol (100% CHCI3, 5% McorvcHch dd 100/0 

McOwCnd' cp.ctir€ly). Furlhd Frifi.ldon by 

sing a E lcling HPLC (L-80, mt r-n tsol 1:1), 

yielded rrc si-pun li&tio$ (f.p3tsl ard !rp3F2). 

"tro, 

tt4io "'|', 

' lrl tz 

r1E puific.tion of ii&tio! Irp3b-2 (13 Ds) by uins a dyclitrs HPIC (C$120 @lunr! 

l0ryo MeOH) atrord.d a trd codpowd 4 (3.2 Be,2.O x l0-rv. yi.ld) (ExFrin€nral, 

S*ion.1.2.3.3.4, Pagcl I5). 

ls HREst-Ms (+e€) show€d thc [M + tI]' .r r/r 551.2133, mponding !o tb€ fomda 

c'HxOD (calcd 551.2123). Thc EI-MS of 4 3horcd ch@knsdc pclts fof cl.odde 

trF tumodfuerFnoid! !t r/z 81, 94, 95 ed 59 Cig. 3.1, Pr€e-14). ln addilion to th6e, 

th. dluglter ioB !l Dt/z rl9 lC$1O\, 356 (CaHrOi), 371 (C!H!OJ) &d 388 

(crH!Oi-) w al$ ob€. !d (Schd€-3.3, P.se60). Th€ (Jv ed IR spelra wee 

disdrtdvcl, sinilu ro cdpouds 2 lrl 3 indi€tiDg tbe prlsme of siFild 

Tle |H-NMR dara (tablc-3.4, P!g.J8) sho*€d sig!.ls for rw n€ihyls, oN nethoxy dd 

frna .in8 prolo6, ch&&lerislic ofcleodeelyp. fimoditerDdDids. Thc do*rfield shiti 

orrh. c'l8 61er ncrnoxy prelm. in cmpoud a (r! 3-85), d 6np&.d 10 2 a r (rH 

1.75), ws duc lo th€ pt€se of 3 @bolyl gmup a1 C-2 &d scn@rion of e 

qtendcd q-

$-nMrumr.d dbonyl sysrstr. Thc 'H-NMR sFcttm .le etlibit d si8tr& for tm 

oxyeeBl.d n€lhind at d 4.39 (brd, J6. 

'= 2.6 Hz, H'6) &d 5 53 (dd'.^rq,tt= l l l Ha 

44n.-6.2 Hz, Hl2). A siDeld.ld6-26 (tl-3) % sign d b th. c-3 oleflic Foror 

fte neilin sisEk at, r.48 (dd, Jlalr= rr'1 Ha Jwi 2.2 ttz, H-8) dd 2 65 (tl.Ioc 

h= 6.5 Hz, tl-10) s@ dE to C-E ..d C-l O d.tbi@ Fold|s, lesp.cliElv Sign b of t!. 

cn l n thyl€ne prctoE appq..tl al r 2.l o (dd, ,Ir14 Ir= 14.0 Hz, i rq D!= 6.2 H2' H'l l a) 

and L95 (dd, Jl 

'r ir- 14.0 rL, J' li h= I l. I Ha H-l lb) ThG pffi of! fitu ing B 

iDf€ftd fiom sign'is at rts 6.50 (d,.r,a,r= 1.0 H2, H{4), ? 50 (! ft, u6= l 5 Ha H-15) 

ed ?.58 OR,II-16). Thc 'H-NMR sierdls !t r 444 (d, J'(f 7.6 Ha Hl)' 3 E0 (dl, 

Jia6f ll.9 Ha J6\!"- 23 l1z, H-6'a) ed 3 70 (d4 JdA 6.= I I .9 Hz' Jtt,5n= 4.2 Ht H^ 

6b) ld sigled b r-D-gltcopyt@stl 3d.lit!t d !t C{ Tbe proloN .s*ilrcd wilh 

ttE suert mi€ty '@m&d ir thc oqtappin8 Fgr@ of ih. sFctud ^r 

H-2' ro H-5). 

D !.I 

J"" 

\ 

6 3.27'3 31 (41t,

Tn€ FC-NMR sF.lrm (Tabl.-3.4, Page58) idi€i.d th. ptEs.@ of27 csrhons, and 

w6 dhtinctiv.ly simild to thlt of @mpound 

200-1. The M.l9 ad Mc.20 apFlrd al , 

@Eting.t,106.2 E Ni8tr d b tE 

oxym€thylm. rpFar.d al d 62,3. 

^ ,t 

S.[d]31: Ms brgmndion po@ of mp.ut a, 

i 

1 

fra|*'onla 

2, *.pt for sn ldditional C-2 sign.l at , 

28,3 sd 21.3. etF.tiv.ly. The carbon 

'|ffiic csbon (cn), q'iiL dE c'6' 

Io derH-'H cosY !p@EM of .dpold a (Fi& 3.1.1, P.g+56), te C-| @thyl@ 

pmioB (rB 2.93, 2.55) sho$rd vici@l corLtn n wilh lh€ C-10 n thire pretoo (& 2 65) 

Cos-pcats wr. ob*red bet{d lh. C-7 ncilylenc preloN (ru2.39, 1,56) with th. C-

6 (& 4.39) snd C-8 (dH 33E) nldhiE Fototr!. TlE Cl I dcthyl@. pret@s (& 2 lq 1.95) 

showd cosY @rcldioa eilb H-12 (rx 5.53). Ce&Fit! b.t$e! H-l4 (d 6.50) dd H_ 

15 (d 7.50) of th. fud nng wrc .l$ obwcd io @nFutd a 

"t 

lk 3.1.1i COSY @frlalim of@nFu.d a- 

Thc lolg{{se 'H ro 'rc inc@tioc (HMBC) of @mFud 4 (Fi8 l 19 snow€d 

@frl.tios of rh. C-l n€lhyl6. protoB with C-2 dbonyl (, 200 3), *bch wd d$ 

@uphd wilh the C-3 ohnnic pbton, IIF HMBC intd&tio6 ir oomPoutrd 4 ndher 

$ppon d it! siniloty *itL odpoud 2. 

ta 

I:. 3.rl: K.y HMBC @Glri6 in @nF0nd a

'nE !t ..ochdilny in .ompou.l .l wd d.duc€d on lh. bsb ofNoEsY @rclaliou (Fig 

3.1.3) b.tea HdMc-Ig, FE/H-lq H-tfi{, ElOMcl9 dd H"l2rI_10. Thrs 

hdic{&d lh, Mc2o, AD-slMPytuosyl d C{ srd frm dls !1 cn2 @ Foddt€d, 

stiL H-8, H-lo, H-12 &d Mclg e.[ o-o.i6l!d Brt d d th€ !!o@ di!.aio!. lh. 

@6uMd B id.ntfi.d s (5x,61,8s,9x,10&12+15,16€poxv-2{xcqp-} 

glucop)te5ytlcleroda.3,l3(16),t+lri6l7,l2-olid-l E-oic &id m.lltvl cater (4)- 

Fi& 3.l3: K€t NOESY ffiLli@ itr 4

T.bF!,a: I'c'- dd I 

H-NMR' ch.oical shii .bla ot conpoud r: d i! ppn .rd J d He 

125,3 

CH 6^t 

c 

2.9t dd(J'.i= tA,9, JhtF 6.5),7,5J d (,rr '.- ll9 I 

a.te d!gN,i r.r,,tn-; t2\ |.se dtQ\-- 

CH l..l dd Lrr r= r r.7. Jr r. 2 2) 

,ro dd-(J,,, 

r- 1..6J,c= 6l)J:95 A o";;;i 

5.5] dd Vqn- l l.l, J'r b= 61) 

' 

c.l5 

CH 

CH 

CH 

6.50d(Jl1r- r.0) 

I!s:v12_-l 

_._] 

23,1 

CH 

CH 

CH 

'Rmrded at 125 MIlz in cDrOD, 

'Rcodld at 300 MHz in CDTOD. 

or!' I 

3llt dd (/.!,t- l1.e,J( r.- 23), 3.70 dd (Ja.r- 

53

3.r.1.15 

It,PAC: 

(1rR,4&5{,6s,8i,9s,10s,1?5}3 J,l 

cl€roda-3,13(16), | 4-irien-l?,r2{[d{ic -id 

herhyl 6l!r 

Ftulion F*2 (l.l g) fton S.phldd LH-20 @llm 

(warei nc0unol, 3: I ) wd subj€cted to evcrsc ph.s 

Ecyclilg HPLC (L-80, wter-@rhel, l:l) to 

afiod @npoud 5 (2.9 Ds, 1.8 x l0 5!6 i.ld) s. 

@lods glMy elid (ExFi|Mt l, Senon- 

3.2.1.3.5,Pagc.116). 

5, l6Diepoxyq&Dsl@ptMvl} 

The HRESI-MS (+v.) of conpoud 5 show.d the [M + E]+ d. n/2 55t2255' 

@ftspondins (J th€ fomula C??Hr6Ou (cltcd 553.2280). IrE EI_MS of@mpoud s 6 

dinin riEly sihi|d ro 6os of c@tDud! l'a (Fig l.l, P!gc3a), wbich slFNd FIs al 

,,/z 19 (c,Jj$'), 16? (GH,,Or), 341 (CIHrOr), 3?l (cnHsoi), .nd 188 

(c,,Hr.ofl (Sch.ne3.4 P!se{o). th. UV ed IR spdn" of mPo6d s w 

@Gistent with th€ new compouds g, ruggening limild tuncti@alitrcs in thcn, 

The |H-NMR sFchM Gable-1.5, Pa865l) sho*d tqo oclhylt otu mcthoxv and a 

nr& rirs. TrF TH.NMR de showd ieo oxygdt d mclhi@ sisnats .t d 4.58 (d4 J6a 

I12 Hz H_|2) Sismlsar,125 

'r-9.1H2,.r6ar=9.5 rz,H{)!d 5.50 Ord,4r&rt!= 

(ov.nap, H-3) \N@ Nienea b lhe C-3 pototr of ihc cpoxid€ ring. Signtls at , 2.60 

(ov. ap, H-8), ed 1.70 (bts, H-10) werc due to th. C-6 md c-10 neihinc Poros, 

6p@1ively. siSn k ai , 2.22 (d4 Jr rq r rr 14.8 rL, Jr r" ra= L8 Ha H'l la) ed 1.80 (dd, 

4 rtr I h= 14.8 Hz La ra= 11.8 Hz, H-l I b) B* aisn d ro the cl I ncutyld. poro6. 

Th. Fa@ of frle ti'8 E '".r!d A@ $gltls at r! 6-52 (4 na r= l 0 H2, H_ta), 

7.50 (t, jr.,tu= 1.5 sz, Hlt &d ?.59 OE, HnO. Th. siFals !r d 4.14 (4.4'(tr- ? 6 

5 

t

IL, ru), 3.80 (d4 .r6,a 6!= I 1.8 Ha J6q rt- 1.9 Ha H{'a) .nd 3 .70 (dA, Ja\.q,i= tt.8 ttz, 

J6rrb= 4.5 Ha HitJ) *ft NiSn d ro AD-gly@pylasyl mi.ty, sltadnt d d C{ of 

te.l' 

a\ 

^ :1.' \^6i! O 

S.[.&J.a: MB 6lgn@|!tiu of @Dpound 5. 

I 

I

Tne ITCNMR sp.ctin of cmpoud 5 shosrd sr8lrls for 27 cirto6 (Tablcl.5, P.ge_ 

63). trhich v@ 6lvcd inlo tuo m.6yl fw€ d€0tylde, ilit€en neilire, tdu 

qualemary, rwo *td dbonyl ald one m€tuxy 6bo$. Two methyl c&bos es@led ol 

, 19.4 Otel9) ard 29.9 (Me20), aloas wilh thc si8lrls for Pretoc of tb. 6rer nelloxv 

,t , 5l-4 (cqMel8). Thc Elarive douneld shin of lh. 6&r carionyl !t Cl8 vs dE ro 

.lcshi.lding @u&d by dns itrajn ofepoxidc, s wll a i[. .l@lronc8!tiv. oxvscn in cloF 

proxinity. The oxyg€n-b€eins C-2 ed C.3 of ePoxide app€acd al d 60 3 md 63 2, 

Espstively. Tne dton wmting ar d 104.9 w signed to $e mh.dc wbot (c_l ) 

In rh. COSY 45'steEM (Fig. 3.1-4), ctBF& s@ obs!.d b€twn H'l/H_10, H- 

lm-2, H'2|HJ, H-7lH-6, H-8/H-? ald C-l I bcthyl@ ed c'12 (dc 71 3) pbtoN The 

NdDtic c-14 n thinc prcton showd @neLtion witl! iI€ cl5 m.thine prcton (Fi8 

3.1.4). 

The HMBC spdt'M of 

conFud 5 (Fie.3.1.5, Page- 

62) showed orelations ofC"l 

dd C-2 rerhyldc protoE (du 

1.5?,2.04, 1.90) wit[ llE 

.poxy $bsritul€d ndlrirc c-2 

(dc 60.3). Th. posiiion of th€ 

4l.r n€lhoxy wa d.duccd on 

Fig.3.l,{: rcy COSY coftlations i.composds. 

rhc bsis of its 8.hitul prebn (& l.?E) cortlati@ wirh rhe c4 qucnE y @bon (lt 

61.2), c-J (rc 40.9), cn 8 (rc l ?2.2), ad orituc ring carbon c-3 (rc 60.1). nE net'iDe 

signals al ,H 4.58 (H-6) ,howed @rclalions wilh C-5, C{ od C-7 (dc 40.9, 78.5 dd 30.6, 

rcsF€tiv€ly). Thc.lmd&€-lr!e nModit€A.n larorc skelebn wa d.dwed with tn€ 

help of sF.t l .vid@s .rd @b!o.ien with dat! of @npoudds r-4.

The st rcochedsrry in conpoud s B d.t mined on tn€ bdi! of NOESY (Fis 3.l 6), 

*hich sho*.d crcsF 13 

b.rGn ll-:t/Hi, l,{H-8, H- 

6/MF20 dd tl-8/M620, H- 

loA,L.l9, lI-12/H-10, lhB 

indi.lrirg llrr lh. H-3. 

ncihoxy@bonyl giow !t C4, 

Me-20, H{, H-8, atd thc tum 

nng rl C-12 de sll 9{riotcd, 

*til. rh! .Fnd. ii4 (c-l/c- 

4), Me-19, FD'gl@ptcNyl 

Ft, 3.1.5: Kcy HMBC @dlatioN in cdpoud 5, 

old H-12 @ sI a.dcntcd. B.$d d i[6c obcdaiioG, th. onpound @ id€nlifi.d a 

(3i,4r,5x,6s,8&9s,1 0S, l2+3,4,15,16{i@ry6(FD-sl@Pt1!NylFLr.d!- 

3,l3(l6),r+ri*l?,l2di+!E{ic &id m.rhyl csrd (t. 

Pis. J,1.6: Kry NOES Y oftlttoB ob$d€d for @mpound 5

T.bb!.s. !'c1ed'H-Nl,'rR'ohdical shinlbt of @mpoud 5; d h PPn adJin Hz 

c{ 

lo'' 

c.tz 

c.lt 

c.ll 

c-19 

ox 

ClI: 

cu 

3t.6 c 

tt22 

29.9 

r.m'ddLe)i I t(n) i 

2.04 (m), r.eo(n) | 

CH 4.53 dd (r{ rF 9.3, J,r r- 9.5) 

CH 

CH 

n coiLd rI 125 MHz i! CDjOD. 

'Reqdd d 300 MBz i! CDjOD. 

212 dd (J'r ,r- l4E J,h b- IJI 

|.!0 dd (r"r 'r= la'q 4'r 'r- I l t) 

3.rodd(J(t' t1.3,.r,\n- lJ} 

3_mddcr.r-- lr.t4rn-.r)

a.r,l.l.6 Ti!@rnDoridc D (6) 

IUPAC: (5l,6{,8s,9r,105,12.t}15,16+?oiy-2{xc6-(&Dgl@py@ylFlsod& 

3,13(16),1+ai.n-l7,12{lid- 18- oic acid methyl €std 

A suttstction BE2 {3j d 

AoD ln. buramlic cxtr&l s 

pannioned b.iweo m.th6ol (Bw2b, 2.1 g) snd t'lt t 

solubl. (8rc2r 70 ns} Thc D.!'eol $lubl€ 6'acti@ 

ehco subjcctd to siLica gel @lU@ .htunElognphy 

sflod€d fou sutstsacdoB (Expdim€dal, Sch@3.1.2, 

Pagc-l ll). SiEil,r ftutiN lioD ibe @ll|m q@ 

combin.d on rh. bsis of TLc nd th. puiticltion of sub- 

ndi6 B@2t12 io 15 (ExFindal, S61i@313.36 P.gcl 17) by Gycling HPLC 

(CSJ2o, I o0% MeOH) yiclded a new compourd 6 (4.I Dg, 2.6 x l0'"% yield) 

The HRESI-MS (+ve) of onpourd 6 show€d tlc M + rll- tr ,1/, 55t.2t71. 

@Gpoodins !o rh. @l6'nr fodda crHlou (cilcd 551.2123). Th. EI-MS sltowEd 

najor fhsment io$ a! ''lz 119 (C.Hro). 356 (croHlo6). l7l (CnHrO6J, md 388 

(cnHlql h addiri@ to rh. s.!hl t|gEats che.ldi3tic or ddodestr"e 

fueodileDo6 (Fis.3.l, P!s.-34). fte W spdtlm sho$td ab$ation bsds at 225, 

216,205 M. TIrc R spdEu ((Br) stFsrd s.r.hin8 fr.qlmiG fo. O-H (3421 cn r), 

c=O (l7ts,1674 @r), rcna1i. dns(1505-143? cm l&d c'GC (1080, l0l9cnr). 

The lH- &d rrc.Nl'R sp@Fd (Tabl€-3.6 Page{6) displayed signsls for two nethyl 

greupsr a .s.r n rloxy &d a fud nrg, .n@irisric of nfrDditlFB. T!. rH- od 

IrC-NMR d!r4 cosY (Fig.3.1.?).nd HMBC cmlstioE show€d it ro b€ simile !o 

@npouid.l, qhich ii a fu@odit rt6. &h.toic, glwyl&l€d aI C{. Ho@8, thc C-2 

posidon h @npound 6 @ ondial s B d.dwd iom ile prcenc. oad.dditioMl

c&tonyl ar dc 200.3. The HMBC 

corclatioq of HJ (dH 2.60, H-10 

(rH 2-92) sd H'3 (rH 6.42) *it[ c-2 

funhd snpton.d th€ prceo@ of a 

kcro fwdoelny in conpound 6. 

Tlc rH, and rrc-NMR dara ol 5 wft 

sihild to thos of @mpoud ,1, 

.x@pr fo.lhe sli8hr difr.lw6 in ite 

Tl. NOESY st ctrum of @npound 6 

(r'is. 3.1.8) show.d oftlaioos b.rwa 

H.6/Me-19, H.6'H.8, Hlo/Mel9, H, 

VMc20 ad H-124l'10. I}e 

indicared tut rhe l-D8lu@pyre6yl 

moicA ar C{ rnd the nlE.irg rt C,12 

@ p{dote4 whilc H-6, H-8, H-lo, H- 

12 Me-19 ed M..20 & a{d.nlcd. At 

this poin! it a @ncludcd itEl 

,-+j6 

Flgl.l,?: Key COSY@mhlioB ofin6, 

chdEcrl shitu dd sllilting patLm. T!. mdr difrftrG we in C-8 (r{ 2.40, ,c 45.4), 

C-lI (& 2.20, Ll8,rc42.4)&dc-20(&0.98,rc2?-9) sisnab.In addirion ioth.c,H-12 

in @mpoEd 6.pFd.d lo bc m@ d€shi.ld.4 lsnlling.l dH 5.78. The ohsplrioN 

suSSesl€d some ditleMc.s in the n€EochmisLa ofconpouds 4 dd 6. 

ty 

Fk-J.l-8: K.y NOESY @Rl.uos in 6. 

conpoud 6 is a 9-cpiDa of4 (Fig.3.1.3, Pago-5?). On ihc b4is oflhe abovc di*usion, 

compound 6 *a ded@d ro h.E tbe sfucr@ (5i,61,&t 9X,ltrt,l2.tll5, tGc!oxy-2{xo- 

6

Trblr3J: 't^' ald 'H"NMR' chdic.l lhii dd! of coiipoud 6i , in ppm ed J h tlz 

c.tl 

' 

P@d.d a. 150 i,ftt; in CIIOD. 

'R@.dcd 

cll 

ar6OO l,fltz id CqOD 

2.t9 '! (r. 'r- 16.t,4^ 'i'6 612nr dd(.r'i r- ldl, 

2.30 dd (,,r n- '..3,4&=3.4),l.7edd(rar: la.r, 

2.a0.ld {Jk r- 6.4, J. r= 1.5) 

2.20 dd (4,( nr- 1.,3,r,,q,,= r.5),1.63dd(r,,r,h= 

CH 5.?3 dd g'r ' 'r- l2 l,rr".= | t 

CH 3. 13 dd (.4r r- 3r, 14 h= 7.7) 

3.ar dd (4r.f r r.3, J& $= l.e) , r.?0 dd (J.r&- | r.3,

3.1.1.1.? Tho6ld. A (7) 

IUPAC: 0 rt3.t 5{,8,t 9x,10t,1zt)-l t,l6-Epoxy,4.Cr-D-glu@ptmosyl>clmd.- 

2,I l( l6),14-rridc | 7( l2),I 8(ltsiollid. 

The puifidrior of fdctio$ BulL5 and BelM (951 

ng) by uine @y.ling H?LC 0/80, wlFtuthdol | : l) 

aforded conpoud 1 (4.3 n\a, 2.7 x loi% yi€ld) 

(ExDerin€nrd, S€ction-3.2.3.3.?, Pagcl l8). 

-Ihe HRESI-MS (+*) of @!oud 7 sho*€d rbc [M 

+ r{' 

at ,/z 521.2043, corcapording to tb. fomuL Cr6HrO| 

(calcd 521.2017), Tlr. EI-MS sho\rcd p.aks rr r/z 81,94 and 95. Hower the liagnflt 

io, ar ,,/2 t9 (C,Htq), @nmon in @Dpoudr 1{, @ missing which indicrred th. 

ab*ne of tn. dd mcthoxy .t C4. The EI-MS ats showd fragndr ioc .r r/, I 19 

(c'H,o), t]4 (Crr.Lq"y G,tr,oo1, 16r (cDrJ,t 252 (c'|H&o), and 3t4 

(cFrirro.-) (sch.mc-3.5, Pase6q. n W sp€rm of.ompoud 7 rhowd absorprion 

beds ar 224, 2l l, 207 m, whil€ lle IR s!@tM (KBt showed sirclching fEqwncies for 

o-H (1420 cm), c=o 0751, 1716 chr), @mlric c{ (1505-1384 cni) ed c+c 

(lo75,lo23cnr). 

The 'I'-NMR spNtnm (Tsbl.-3.7, PageT l ) showcd rst .rr coupt d olcfinic polos at ,! 

6.61 (dd, t.f 7.2 H:.1 h.6= 4.6 Ha H-2) erd 6.81 (bi4 4. r= 7.2 Hz, H-3) d!€ b C-2 dd 

C-3 oiefitric proloE. A doMfield brod .roublcr at ,! 5.30 (.4c ,= 4.6 rL) ws Nign€d 10 

oxys@t d Cl mcrhin. prcro!_ nF rH-NMR .xnibit d a double .toubl.r .l , j_56 (J|rq 

ni= 12.2 Ha J&rt 4.1 Hz)L de ro rh€ Cn2 oryge.ar€d meurift polon. SigDals ar, 

2.57 (ov€ ap, H.8) &d l.8l 06, H{0) w@ dw ro rh€ c,8 dd c_10 nethi@ polos. 

Signals 6or.ti!g at , 2.39 (dd ha nt'= 14.7 t11Jn\E= 4.1 Hz, H.lh) ed 1.98 

:I

(orqlrp, Hl lb) *a ai8tr.d to rh. C-l t 

C-7 ed C-8 appc.rcd at , 1,94 (n, H-6r) 

lo.l 

f" 

Tne signals dpp.&ing at & 6-55 (d 4{ B= LO H2, 

H-14), ?.50 Ol! Ha H-15) ed 7.59 (b6, Hn5) 

rw Nigned to thc NElric protoG of r Rtu 

dns. T 

\"\.1- 

h. 'H-NMR sigul5 et , 4.71 (d" JrL2'. 6,1 

tfa H-l),3.81 (dd, ./6,q 6r- l l .9 Hz, J6a,i= 2.1 

Hz, H"6'a) ed 3.65 (dd,.,f6!.6t= 1r.9r.,.J6r.!i 

1.49 (n, H-6b) 2.55 

'c 

o-= b 

SctdG3S: MG frgDc m@ p.tlsD ofo@pourd ?. 

I''BpooahP' 

Trc Nltyl@ ercu!6 at 

(ovdllp, H-?a) &d 2.08 

rx) 

v"^ 

63

5.2 H2. H-6 b) lw bsiened to ,-tlglycoprddyl moi€ty, subsrilutcd at C4. 

TIE rrC-NlvR sp.crruD of @b!ou!d ? 

showed sigMls fo. 26 clrhds (I!b1a3.7, 

Pag€-71), itr luding tw 6sule @tbyl3 

(Mr19 md Me20), 6ns ring and pbloG 

oi ihc l"D-gly@pymosyl moicty 

chmclerisdc of a cLodaeg?e 

nmoditdp.rc gly@si.l€s. ThE 

belhyla. c{bon signais al ,27.1, 18.5 

olt 

Hg. 3.r.9: Key COSY corchtio.5 in 7. 

and 42.3 wrc Nigred ro C-6, C-7 drd C-tl,6p6tiv€ly. fte 'rC,NMR sigals ar, 

176.7 dd l?5,2 ww due to ile esrd C-17 {d C-18 Qrbonyl anbors, r.sFclively_ The 

doMfield shin of C- 18 6t.r @bolyl @bon w dE b 6,letom drg fomdod betw 

CIIC4. The olcfinic C-2 and C-3 .lpcstd d, 131_7 and 112.5, Esperirely. The 

oxys.n-b.&irg lcrri.ry c..boB ^'.4ks.d ^ 

6 74.8 (c-1),72.7 (c-r2),75.1 (C-2'),1E.3 (C- 

3), 7l .2 {c-4 ) ed 78.0 (c't). Quienary cilbotu ar , 87.5, 40.0 dd 36.2 w.E bsisned 

lo C4, C.5 drd C-9, Gpecrively. The Ebon Esnrling ar d tol,5. wd 6sign€d to lhe 

oom.dc ca6on (C- l i), while th€ oxymeAyl@c C{'aplarcd a1 , 62.5. 

L dt t|rH COSY of 1[.ompoud ? (fi& 1,t.9), cGF.rs B@ sn b.twn C-l 

(& 5.10) ed c-10 (ru l.8l) nethirc prcroN &d rh. c-j ol€fdic polon (, 6.81). .nE 

olefinic proloft at c-2 (d 6.61) ed C-3 (d 6.8!) showed coftl.tioG w'rh ceh orhd. nr 

C-2 olcfinic polon ws in lm rle @uplcd io thc C-t m€lhin Fo1o, (r 5.30). fte rH,rH 

COSY spatruh ale sho*€d @relarioN bct*a H{/H-?, H,81H-?, H-l l/H-t2 md H- 

14/11-15.

Thc HMBC s!6um of cmpoud 7 supPoncd the basic sk ldon of thc clmddetvpc 

funtuditcrpd.i s s in @npounds l{. Thc key HMBC @clalio6 in t 9@ 

b.tl|fu C-l ad H-2, H-3 .nd tl-l O. ftc Po.ilron of dtc ADglycoptreo$ *a d€d!@d 

oo th. b6's of @ftlsrioc ofth€ aomctic pDlon (H-l', dH 4 71) with the qulenDrv C4 

(dc 67.5). The posin@ of th. .a'tdyl al Cl ? M inli'r€d on rh. bat ol €ftLtioa or 

tlE C-8 D.lbite pdon (rx 2.57) witt c{, C-?, C-q c-l? (& 27 1, l E 5, 36: ad l ?6 ?, 

Gpetirely). nt obonyl cdbon. csatiog .l ,. I ?5r. displatld crcs-F*s tiih C'l 

(6.E1) and c-(rH 5.10) n€thine pre1ons. IIF cl.bdeetyF ireodit rFm leionc 

slcleron, s stom in Fig, L L9. 6 deduc.d nom this d,r! 

IIF ar.l@hdisry in.onpoud ? w d.tdnincd d dE bai! of NOESY inLtutios 

(Fi9.3.2.0). Ttu @rcLtios bet@n Hn/H-10, H-10/MFI9, H.8M.-20 and H-8/H-10, 

H-12lH-10 ildiclr.d thd H-1, H-10, Mc-19, H-8, Me20, H-12 .nd ,-D-ejMpFeosyl 

e rll a{d..r.4 vnil. fi! laroE .i!s.l Cl/C4 .Dd fitu ring .l C-12 e F{d@tcd. 

On lhe b6is ol UF $€ir l dila th. @dpoud w d€de€d to b. 

0x.4s,5n,8,t9n,10,t,12,5)15,16€poxy-4-(l-D-glucoprdosyl){ldoda-2,13(16),14 

rriw{7(12),18(l){iouid. (7). 

Flg. J-2.0: ]

T.bb3.7: '3cr- &d 'H-NlvtR'cuFiql lhin dd! of@qoudl 1 d in ppm &d J i! Hz 

'R".ord.d 

2t.l 

CH 

CE 

CH 

.t 150 l'fltz in CDTOD. 

'R.@rd.d .l100 l,4lz ir CD3OD, 

23e dd (4h !f 1..7,4( 'f a.lI 

r 56 dd (r,L 'a- r!.2 J,r,,= a. r) 

CH r.2e(dqre) l 

r.3 r dd (r46f | | 9, ./.r r!- 2. r), 

3,55 dd (Jq &- r 1.9, J.'n= 5.2)

J.l,l.l.8 Bonp.l6id. r (E) 

IUPAC: Methyl (2j,6s,6.i,9x,10a.t,10b5!2{3-nay}6f'De1@P}1dosyl_9_nydroxy- 

5a,l otsdiDelhyl4{xon.4,6,6r,9, l0,l0a,l0b4blydro-2lt-b@t ischromc?- 

A ferion nob th. bdelic dla.t, Ftp2.-2 (7 nsr, 

B puified by ui!8 Fy.lirg HPrr (GS-120, 

10e,6 MeOD 10 oblain ! Fw @mDoud E (3.7 F& 

2.3 x IoY. yield), s ! @lorld 8l|@y slid 

(ExFrinEt.l selim'3.2.3-3.E,Pagcll9). 

The HRESI-MS (+v.) showed tM+Nal'at ,/z 

573.1980, ocpooding to th€ fmula CrttlOD(calcd 573.1948). TlE glyGidic natw 

of 6 w6 infcf,ld fbm EI-MS filglMrali@ *tich s[o*€d a Dat lor the asly@n Doiery 

at ,/r 388 whjc[ 6 di$ by tte los of a', 162 firb [M + Hl', 

rte pltsee of 

'ndicllins 

a h€xose noiety. 'ftc frlgndrs "a", "b' dd "c", cbmct€risric of a i@ @iety, 

apl8ua ^ az El,l4 ad %, resFclrvcly (sch.b63-6, Pags?4). The IR sFcEm 

dbpbyed .berpti6 .1 1430, 1725 ald 1664 .n r for 4tl, .sta c.rboryl aid enr.ric 

nlg tumrioD.lili.E 6Fdivdy. 

ft- r.{, -N 

TI€ rH- &d 'rC-NMR lp.ctrz of @mpoud 8 (Tsbl€-1.8, Page?5) shoved the pEwe of 

ttu eg'ne nethyl goupq wbich tellr.d al & L45 0.t€-19, ,c 23,9) &d I.l2 (M€,20, 

4 27.4), beihyl 61a preioc ar & l-76 (CqMelE, ,c 52.3), rnd th Ei{u!6ri .d 

doubl. honis d Ar 6.40 (& 138-5, c-3;4 141.5, C4).nd 6.9a (r. 140.9, c,7; dc l3?.0, 

C-E). 11 also showd ilF ch@ctdislic siendk for pot6 ofa nutu dn& 

,IlE rH COSY spcctrum shoved @lptings bcle.cn de cl oxyrndhin sicral (d 4.52) 

c-2 olcfbi. prelon (r 6.94)- Ilc c.'!i@l D.rhir. a1G2 (d4.35) ald tl|e ol€flic 

L

oton al C-3 (t 6.40) disPbtld vicin l colpling Th. oftlatioB b.t*etr tlE c- l I 

hdhyl@edtt c- 12 G6i!e rrclos wG ds ob6srcd ir lbc COSY spatu 

Th. SMBC co@Ltiom b.t*.6 C-l2 orym€tl nc preton (rH 5 24) &d C-13 indidled lb. 

orcsce of a ilm hol.ty !l cn 2, *hile th. 'r'J c'rFp€ak of th. Cl2 nctline prelon 

with C- l? a'd c-q ddg *ith lhe r, @cLti@ of th. C-7 oldbic tulbi* protoa (4' 

6,9) wifi C-l? sugg6t.d th. prffic of a six- ndbqed lacloE bawd C-8 and C- | 2 

Th. sD.chl data of E ws in f&i clo* to that of a knoM @mpou4 bomFloside F 

lM.ni4 T. S., 9l al,, | 961, qc.pr fd e ldditioad hydroxyncuirc signal at dts 4-51 (& 

64.0), *ticb s signcd 10 th. dyg@l.d nEihiF C-2. 

The pt.e@ of a p-glu@pr@yl mi€ry wa inf€ned fiod thc NMR data (& 105.?, d, 

4.41, 4r zr= 7.6 Hz). Th. lintrg. of tbc gl@prl@ryl Doi.ty io E M del@i!.d to b. 

al C{, b.eed o! irs chdical shin(& 8l-l). In rt rtl-NMR s!@1ru Gable-1.8, P.ge 

85), tn couplins conel',r (.4,q,r= 7.6 Hz) of rhc doheic prctoo (& 4.41) indi@&d a /- 

Th. st @cbeni5Ly i! @pourd 8 B d.du..d @ lh. hasis of ROESY .xFimr Th. 

cbsFals indi@td rhrt H-10, Met9,H-12, Oll 4 C:2, at f-r}slucopymyl @icty 

\

.tC{e.I a{naterl wbjle M620. H-5. H-2. llh.truingalGl2@${ient d 

B$.d @ ihdc $61nl 

dala lh. orEtrc B d.duocd a boEpcioide I (8). 

scldFL6: M 

O 

Dr$ nrg@llllid in c@poud &

Rdtha'dDttMtd 

T.Dr.n* "C'- ed 'H-NlviR'cbmicd ltift dd ofcobpoud q d in lfd 

c-1. 

t ,5 

,!: 

11r2 

52.1 

?t.l 

CH 

'rH{fr(4 

t/o dd OL '.. 1.4 i( h_ 3.3) 2 oa dd (dtllP) 

CH Jla dd dr ,,i l l a, J,& ,,,- 3.n 

CH 

CH 7 

CH 

'Rccqrlcd at l0O MHz in CDTOD. 

'R6d.d 

.r 300 l"trlz in cDroD. 

l.l2r 

r.l7 d Q4 $- 7,5. Jal; 7 -9) 

3.19 dd (/4 rr- 91, J4 n- 9:) 

Thdt$tetsrd 

.nd J i! Hz 

J.r5 dd (J( 3f 124 4\ '.- 2.0) r-?0 dd (J46- 

|

t 1.1.1,9 

IUFACT Mlrhyl (21,6s.54x,10.s,10bs)'2{3'fr!yl){_FD_81@P}1@svl-6a,l0b- 

din thyl49doxo. I J,6,6a9,1 0J 0a, I obdt lydrG2H_ttMldishrcm.D._7- 

Th€ puiicaton of fd.riotr Frb-l (5.7 g) by @yclitrB 

rPLC (CS-320, lovl. MeoH) lfford€d dnponnd 9 

(l.l og,6.8 x l04ryield)sacolorles gmny $lid 

(EtFdncdd, Sedon-12.1,1,9, P.gel20), 

coftloud t hN ttt Dol*uld fomula CrTEr:or 

bos.d o! its sREsl-MS (+ve), which shoe.d th. [M + 

Hl' ^t "t/z s49.1916 (.o!.d 549.1967). The slycotidic 

natuG of 9 M infcd€d frod ElMs 

fasn€ adotr which sho*d a p.ar ,,/21E6 (c2tHdo1') rot ttu Êlt o! dE b tne los 

of '/z 162 liom [M]', and iidiqrd a hex@ sued. The bsic l6s fdsn.nis ( t', "b ' 

dd't"), chmcteristic of tutuodilerFnd, appes.n al,t/z 81, 94 &d 95, eFctivcly 

(Fis. 3.1, Page34). Tltc IR spe$h displsy.d abe+tion bonds al 3425,1123 6d t667 

cn ' for -OH, wbonyl dd Nddtic ing nft{on lili.s, rc3P€ctively,

compound 9 sho\ttd th. sLwlurll f€4tu6 sinild to conpoud 8, dc€pt thd 'rc-NMR 

sternm of 9 sho*€

T.btF!J| rrc'- &d 'H-1,\4R'chmiol 3hift dlrl of c@Doud 9: , in ppn .nd.r in H2 

c4 

rc-t 

cnt 

cn2 

olt 

c 

CB 

CH 

'Reo!d.d .l l0O MrL h CDTOD, 

'Rc@rdcd at 500 Mnz io cDrOD. 

6.31| i 

227 Viw- ta1,r&6=3.7), 

2 06 dd (J' r I4.r,, !. ,,= I L7) 

'A '.= 

5:l dd (J'! Lo- I L7,./in n"= ].7) 

1.35 dd (/ft.f I l.7,Jas= LII 

3.m.! (/.1r- I l.7,r.ar= .-0)

3.1.t,2 

3.1.1.2.1 

Kmwn Cotrstituert! 

Compobd l0 6 i$lared Aom ilE bulaDlic.xltr.t 

of Z .rispa (ErFrimedal, S€tioc3.2.1,4.0, P!gc- 

l2l) s a y.llowish gluMy $lid. ft. IM - Hf s.s 

ob@al at n/, 5s1.2129 in HRFAEMS CvO, 

whch ws ir agr€d€nt *ilh th€ @l@lq tomula 

CrHlOtr (colcd 551.2134). Its IR spcciiM show.d 

Y'r-+"" 

ch@ckrisdc absoatons al3420 (oH) sd l?15 cn ' (c=o). Aberption bod dl210 m 

in $c Uv sF€trun i.di@i€d th. pGercc of ! @njrgal.d systeD in the nolsule, 

hc |H-NMR aetru 

of onFud l0 sho$td oxygad.d medirc sicEals at , 4.51 ( I H, 

rd. Jr-t\F= E-1 lta Jzi- 3.8 Hz H-2), 4.57 ( I H, b(d, Ja - 2.6 Ea Hi) ard 5.53 { 

Jri< r'r= ll.l gzJlark= 6.1 Ha H-12). Tlt C-2 Foton 

I H, dd, 

shoa€d vicinal @!9li.g eirh a 

doublet d d 6.40 ( ltl, 4 - 3.8 Hz, H-3). Th. C-12 prcton shovEd vicin l @'lplines wilh 

Ct I melhyl.ne potoN d i 2.08 (dd, 4 r( r rr 14.0 Hz J|,a ,b= 6.1 Ha Hl l a) dd 1.98 

(dd,rrr,Id= l4.o Hz, JlrA tr"= l l.l Hz, H-l lb), Th€ IH_NMR sFctrm ofcompoud l0 

also displayed sienals lor iwo angule D.thyls 6i C-5 (, 1.55, 3H, s, Mel9) dd c-9 (d 

0.96, lH, s, Me2o). The |H-NMR sicnal st d 3.?4 (3H, s, CO?Me) m Nigned 10 lhe C" 

l8 stcr eethoxy, The !rcse of a ir6 iinS I support d by rloetn€ld sienals at , 

6.50 0 H, 4 41 6= l.l Hz, Hl4), 7.50 ( | H, r, ij. rl|.' 

| .6 trz, H,r 5) ed 7.58 (r H, s, H- 

16). A m.lhirc doublet ar d 4.41 qirh J v.l@ of ?.6 Hz s indiciliE of a 4o- 

gl@pyMyl miety, cithd a. C-2 or C{ [Fulnd!, 

N. d, ar, l9E6]. 

Tli bMd-bqd decoupled &d 'rc-Nlvfi, sp..rM ofcompoud l0 showEd siSrals for 2? 

6boN, inchding si* qua&nEry, foun€. h.Uinc, fou nethyloe @d tn@ n.lhyl

.dboro. ft. do*nfi€ld signals a1 d | 26.0, 109.E, 145.04 ed l4l 0 wre aine.d to C- 13, 

C-l4, C.l5 .rd C- 16 of a firo ring, Bp@liv.ly, substiluted ar C_ 12. ft€ .st€r abonyls 

C-i 7 and c-I 8 app€&€d.r J l ?8 4 ord 169,4, Espdi\ely fh.'rc-NMR 3i8 l for $c 

oxy8d.Ld m.lhir€ arFied at,64,6 (C-2), 80.0t (C-6), ed 71 9 (C_12), *ltilc r sisnal 

st d 106.3 *s Nien d lo l!. a|@dic c,l!o! of&D-sluoptmsyl noicty. ConPoud 

loBth6id.nlifi.dsrt troM @poud booFld{d. B tFuhda" 

N. d, dl,, 19861 d 

ln. baiis of spdral data (Exrsihdll, S&lid-3.2.3.4.0, Ptgel2l). Cobpou.d l0 ws 

se.n d for 6di.sl svoeing &tiviiy, .!d fouxl lo be inacliv. ,eriNl lh. DPPH 

ndicak lcalin, A., er ar, 19981. 

!.1,1,2.2 Bonp.r@idcc0t) 

Compound U M obtaii€d ftom te$@ FFl2 (3 g) 

of rh. buEnolic duet of Z dipo W rF'inv. 

@lum clrcMbenphy d sili@ g.l (ExFilEdrl, 

Scclion-3.2.1.a.2, Pac€-l2l} Th€ HRFAB-MS Crc) 

of coDpoud ll showed thc [M - Hf rt ,'/z 

535.21?9, consponding to rhe fomula CrHaOrl 

(slcd535.2185). 

Cohpoud U sbosrd tbe sp61al faturcs" idctrtical b to$ of boryetosidc C tlDodcd 

c.rlid lM.llia T. s., ,, at, 19961. Th. 'H-NMR sperun of (FxF.im .l, Sario!- 

3:.3.4.2, P.gcl23) showed distiBriv.ly sinild !p6td data to @bFurd 10, qc€pt for 

rh..pFrue ofs addi.ional sisDal .t, 2.38 (2H, m, H-2) @Eslondiis to th. C-2 (, 

24.8) hcilyloe carhon. fte dgule nahy! (M&19 ad Me-20) in compound ll 

appcd.d ar d l.4l (3H, s, Mel9), od Ll2 (3H, s, M€-20) Tle overallspdtral dd 

phydc.l .L1! of ompobd ll B @6ist!nt wirh th. d,ra Eported i! liLrat@ tor 

"l

@pct6id. C lMdli!, T. S-, er d., l9%1, stic! B pdioNly iqr"d ton I .'t e 

Ir ha h4tr tclr.d fof irs efr61d ita DPPH ndicdr by ]{lqand! cavir dd @wrLE 

in 19998 lc.vitr, A., er a1,, 1998], It M found to bc mytobri. ag.'!51mmd (lT3) 

dd dq (PC-3) ell lircs (cbapter4, P6g.- 145). 

3.r.133 BonperGide G (r2) 

CMpourd 12 w i$lst d nm F$3b-l (97 Ed slE 

t?.rior of lh. b{t lolic srra.l by Bilg Ev.e Pbt$ 

Ecycling HPLC (L-80, l:1 E O,^,€OID ar lhc 0ov 6r. 

of 4 hUnin (Exp.rindial, Sediodl.2.3.4.3, Poge125). 

fb tM + Hl' in HRFA&MS Gv€) apdtld ar n/z 

551.212q @GFnding to thc foroula CrHlO't (c.lcd 

55t_2123) 

'j%. 

TlE rrC-NMR sp.cEu of @EFund l, 3howd sienals for 27 c.rbo8 witb f@ 

q@t n 'y csbor$ C4 (, 155.7), c-5 (43.4), C-9 (r 36.4), and cl3 (, 126.E); rhirre€n 

6.ihi!e wboB, C-r (d 134.2), c{ (d 77.9), C-8 (45.4), C-10 (6 40.7), C-r2 (6 70.1), C- 

14(t 109.5), c.r5 (r r,r4.8) c-16 (r r4l.3), Gf (d 105.8), c-2, (75.4), c-1' (617.4), C-4' 

(, ?1.t, ald C-5'(d 77.9): fNn thylcd, c-l (r 36.2), c-7 (r 29-0), cn I (r 45.J), ed 

ci (, 62.3)i tbE nctlyl c-rq (6 27.4\ C-20 (6 27J), alA cq!{g (, s3.2); ! rdo 

greup, c-2 (, 200.8); .'d re €srcr caio.ylr c-I7 (, 1763), ald c-I8 (, 158. | ). 

ComFund 12 shov.d a dislircrly simil& TH,NMR dgls (ExFrimnral, rlgcl2t ro rhat 

of coftpourd {, €xceF for the slidt va.iations in dtc chmical shins of thc dgul& neiiyl 

goups.r C{ {(, 1.66, 3H, s, Melg) &d (d t.65. 3Il s, M€,19), rcsFclivdy} ed C-9 

{(, 0.98, 3H, s, Mc-20) !d (d 0.83, 3H, s, Me20), Fsr€lwly). mis clEngc in cLnicil 

shin !du.s ofM.-20 w dE lo diffG.! dd@hoisry a. C{. Ans enpsison of ID 

31

and 2D spetFl .lrL with th€ Eporkd d.tr [Fulad4 

N., ,t d/., 1993"], conpoud 12 M 

id.dificd s bodpevEidc G, wlich 9s dlid ilolated &on I .rispa. ft 6 fourd to bc 

ina.tiv. agaist is DPPH adicil srcoging ey [crvin, 

3.1.r.2,4 Bor.p.torid. D (lr) 

Conpoud l3 w6 i$lded Aod 

extn l by sinS @ycliry HPLC 

(cyr20, tw. M.orq 

(Exp€riidt l, S*{ion-3.2.3.4.4 

Paser26). Ill [M + H] in 

HRnM-MS Cvc) appelred at ,/z 

69?-2708, @rc3ponding lo tbe 

fomuh clHr6otr (calcd 

69721t3\. 

A., e|' zl., 19981. 

Buc2b-16 !o 20 {419 me) sutsia€lion of rh. bulanolic 

t7o-.rt 

The |H-NMR sFcrtun of mmpoud 13 showcd dowfietd sisn ls ar , 6.52 ( I H, d, .ft, $= 

L2 Ez, q- l4), 7.41 ( I H, t, ij. (= L7 Hz, H- l5) ed 7.59 ( lH. b6, H- | 6), chdeierisric of 

n@odir€rperc l!.lon.s, in addidd 10 a tulhitu Eiplel rriplet at 6 1.Ot (h,f 3.6ltzl of 

C-3 olefric prlton. Trc dgul& Dcthyls, .lldrainic of cldod@.iw. djrcrF6, 

appc&d al 61 1.30 (3H, s, Mel9) ad l.3 t {tH, r, M.-20). Trc do$t.rs al , 4.l9 0 H, d, 

J|,4,!= 7.4 Hz, H4ra l) dd 4.34 (lH, d, i"q,r= 7.7 rra clc t") wrc &!ign.d 10 

momeric C-l'ed C-l" prcb6 of disecb&id. hoicly, @sp{tiv€ty, The presn@ ofr 

lactone bctwen C-6 dd c,8 ws infeEd fiom rhe downiield sisnals ar rc 180.0 (c-t?) 

lMani[ T. S., a di,, i996]- Tl'e sper"l d.ra of@mpodd 13 (ExFi@rtal, p.Bel26- 

| 27) 6 fourd to b. idcnrical to $d of boErloside D tMadn, T. s., €r 4t, 19961, *iich 

32

ws pBiosty i$lalql fFn I oitP. Conpound 13 3lbqed lC$ valE of95 1410 30 

e.! >l OO pl\,Vnl againsl PC-l ad 3T3 ell liNs, BFctivelv (CnaPt'r4, Pag'-145) 

3.r.1I4 Aon!.lo.id. A (la) 

ThG fr!.rios non dE bulatolic.rF&li tFl2 (3 s) (ExF ine'r'l S'nm3 7, Ptgc_ 

106), Ml (l?0 Dg) (E4einot.l, S@don-3.2 3.4 5, P.gel28) dd Bu2' (55 ns) 

(Experimt l, S.h€F1.1.2, Pdgelll), by uilg Fvclitrg IIPLC (L80 ad Gs'120)' 

aflorded conponnd 14. rr5 HRfAB-MS G!.) chowcd th€ IM ' r\ ^ t|/t 5312050' 

on€spondins b the fomda crHqotr (c.lcd 537 20s0) 

Th€ rH- and rrC-NMR sp@tra (Exp€dncni.l, PagG{28) of @npoud 14 ws id4lical !o 

borapebside A, which M p€viously holatd fom nid&dto /iva lFukuda. N. er dr. 

19861. A .leuiled maltsis ofth€ "C-llVl spettun of bo,up.roside A (r4) r€ved€d thal 

$e @nai! asg@dls w@ diff@t liom tho* EPod.d dlir, particuldly the .henical 

3hitu of Me-19 and M*20 tFutord4 N, 4 41., 1986l T[is su€g6tcd a difcEnl 

s:r.lwlEDjsEy.r rb. A/B drs j@tion. I! oda lo lglw lhis dbiCxitv,2D NMR 

rDcFa sw $died @6rlly. Tb. HMQC .nd HMBC sa@!a indic.r.d rhar dE .hdi.al 

shift Nigmalt of tb€ Me 19 aad Me20 ft.d io b. aviscd ln lhe HMQC s?euun, thc 

prolor s8IEl a1& 1.21 @@l.ted *iO ih. cdbon signal !l & 18.2, vhile in dt HMBC

speiru, th. preton sigtrd .t ,x l2l B @@lded eih itc qrtDr siSlab !t ,c 4?.1 (C- 

5), 81.6 (c4), 76.6 (ci) dd 180.0 (Cn8). Bed on tbis d!la, tn! Bklal .1tc 18.2 m 

ssigncd to Mol9. Corcspondingly, tn€ p.otor siSDl al ,H l.l0 (c@latilg with the 

carlon sisnal d dc 13,3 in dE HMQC tFcuuo) cmlol€d wit[ th. caftor sis!.ls at dc 

45. | (C-l i ), 36.1 (C-9) and 48.I (C-E) in dE HMBC sp€tnm, hdieting lhnl i.h. sigorl ar 

dc ll.3 @ dE ro M.-20 [Fultd4 N. e/ at., 1986]. Compound 14 dbprayed IC$ valu6 of 

>100 FWnL agaid borb PC-3 ed 3T3 ell lies (Ch!prd-4, Pagc-l4t). 

J.1.1.2.5 Bonp.torid. F (r5) 

conlourl 1l ws ielot€d liom Sub-Ardon 16-l (500 ng) of tI€ burdolic *tret by 

6ins @yclins HPLC, Ic-908 (L-80, r : I H2O/MeOH, 4 Er_/min) (E4din nhl, &dio- 

r.2.3.4.6 Pagcr29). Irs HRFAB-MS (,re) slDw.d lhc tM _ Hl- ar â/z s)7.zo2r |]hiqn 

B in!s@mc wirh the Dolcut& fodul! CrHlOr r (c.tcd s34_2021} 

l5 

The rH- ed rrC-NMR sFcl{a of 15 (Experimdtal, pa8.- 129) showed rhe peence of rwo 

aBlle hethyl s@ups or,H 1.42 (Mcl9, dc 25.3) tud l.lt (M._20, dc 2?.1), csrer 

rErhoxy dr r! 3.70 ({O!MclE, ,. 52.3), ard rM rd$bstitur.d double bo0G ar rH 6.65 

(r. 141.0, cJ; dc Il7.E, C4).ad 6.EO (rc 138.1, CZ, rc l4t.?, C-8). rh. p6.trc ora 

fi@ rins ws irlmd ftom liic siena]s a1& 125.4 (C-t3)i t09.7 (rH 6.5D (C.14.); 144.9

(rs ?.49) (c-15); dd 141.4 (rH ?.59) (Cl6). Thc o..utl!N of @ d,Fuen['lad 

wbo.yl and .6-le1on (C-8/Cl2) \r@ d.ded by the HBMC coftlaliom ofH-l (dH 

6.65) wilh C-lE (dc l?0.9) ed H'7 (dh 6.80) with c-17 (rc 172.0). 'It'e pl.sm. ofa & 

lelorc w6 de supgort d by ln. cbtiv€ly uplicld cbmical slift ofc-17 (r. l?2.0), dE 

10 lega ri.g size, s @mpard ro tlE t-j,.1orc rinS (Pavia" D. L-, .? ar-, t9791. Th. 'H, 

NMR sis.Ab .t t6.51 (H-14), 7.49 (Hl5) &d ?.s9 (Hl6) w lrdbured 10 lhe tur& 

rins proroB. the HMBC €orcbnoa oroxymdhine Hl2 (r! 5.22) with Cl3 indicared 

rhe suhriturion of a tum noi.ty .r C{2, qhitc the 'r.tms-p€.ks ofH-12 wirh C-t ? ald 

c-9, rlong eit! Ilre rr J or.latios of olefinic Delhift H-7 (rx 6.80, 4 4 6= l.? rjz) virh 

C-I7, suggest d rhe peme ofa six-oenb.ed l@lon€ bctwen C.8 dd C- t2 lManin, T. 

S.. s, al., l995r Martin, T. S., dr at, t961. Thc sp€rat ttab oflS *s in fd idenlical to 

$* of a tnoM onpowd, bodp.loside F lManir! T. s., er a/., 19961, *tich 96 @lie 

ielaild ton t d6pa.11 hrj beo !.e..d fo. irs amionds! wh.E it rc found b b€ 

imctivc in DPPH r.dical $av.nging say lcalia A,, ar al, l99S]. 

3.1.2 Aporphim Alkrloi& fron Tinotpon obpa 

Ore ncw 16 ed five kroh .porphinc dllaloids l7-2t hav. bM isotal@d fton Tinorwra 

crbpz. Th. imdododul.rory lrd cybroxic aclilirjca of conpou& l? sd t9 Mrc ale 

dermin d duins rhir study (Cbaptd 4, S€rions-4. t ed 4.2. pag6_ | 45_ r 5O). 

3.1.2.1 

3.ll.t.l 

IUPAC: l-Mcrhoxy-2-1/-D-glucopy@yt{t33)Ep,D-gt@pytuosyl}-t

-*v*L 

Puilicat on of ii&tion Bwl (5.6 s) by rccydbs HPLC (GS-320, 10070 MeOH' 5 

niunir) yielded conpoud 16 s ! *hite posd{ (Expqim.d,l, sdtiot-3.2 3 4.?, P.8e 

l3O) The Uv sFclrm show.d absorption bsds at 272 dd 2ll m, ohde&ristic of 

apo+ltnc atatoids [P&ha]r, P,,.t dl, 192; M.e.hdy, M D, e, ai, 1995; Nozt " T, 

d al., l9E7l. Ibe IR sp@irM 3howld srE&hing ftequaciF ar 3426 ed 1660 cd_r for 

hyduyl g.oup and ts& carbonyl Esp€dively. lis HRESI-MS (+v.) show.d dE lM + 

l{l' .t r,, 62o.2lt | , @Eslotrding b de fomub C{tlrNOD (calcd 620 2343) 

TlE rH-Nr,rR of @mpound 16 Oablel.l.o. P.se89) showcd a th&!-pm!or si!8let.t d 

3.?0, dsigned to th. C-l Delhoxy group, Tne multipleis i.lhe doMft ld rgion oathe 

sFcr@ (, 7.24-?.30) werc siencd 10 C-8. C-9 md C- l0 po!o6. Two si4lels ot d 7 07 

0l-3) 6d 8.24 (H- 12), .nd a

).92 Gn, Js.6f tz.l 14 J6a ft= 1.9 n ) &d 3.69 (otna9) '!d 

3hift sicrn s *@ md. d rhe b6c of llMQc, cosY ,d 

TIE bo..t-b€nd d@uplcd "C-NMR spetrM of onpomd 15 (IabL-3 1 0, Pt8eE9) 

sbo*ld dmrtc qulr.nE y.rtbols rr, t4?.3 (C-l), 12E.8 (c'ta)' 127 7 (c'lb), 151 ? 

(c-2), 130.8 (c-3.), l3?.4 (c-?s) dnd 132.5 (cn ld- Th. rrC_NMR.lso snovd sienals 

for fivc Nmaric carboN; C-3 (, I16.9), C-8 (,1293), c-9 (,129 0), C'10 (d l28 l). dd 

C-ll (,129.4). Ir@ m.thyldc @boG.r,42 2,50-8,62.1ald 62 5. w& Nisncd io 

C4, C-t, C{ ed C{", cpelircly- ft. F.lon 

of tlF mide fwliotrditv agF Ed a a 

siryla !r , 8.24 $tilc tF lisn l ar, 4.81 ws ,ssis!€d to H'54 Th! c&ton sistEls d 

' 

I02.0 (Cn), ?5-9 (C-2), E 1.4 (c -3'),7r.2 \C4'r,18 2

d6tu .n Th. h! Eoidi.. h lh. rt$.ddld. rns ftuld to b€ /-D-gh..ptrd0.yl on 

e br oacoq[4c.ddffE ((I.. rFl) td 50 E (cL" Fr') of rb 

'non..ic Fotd Coqound 16 ru tu cld.tabd .t l-te.r2.{AD 

shcqryrl(l-3)tDdqytsrl)6e@0erylltu 

aa

T.01ts3.1.0! rtl'- ed Itc-NMR" chcmical $in dd! ofcotnpoud 15; J vdws i! tlz 

DcEo 

CH 

t30.3 c 

tJ2_t 

ifr/Fl 

CH ?,30(!) 

CH 

1f"1,5' *',:"'::::'" l' :_,1 

!.r5 dL (4. r' 12 5, Jr a 3 1{.- l ?t rre d 

g$$- l2J. Jr._ 13) 

.j(Ntc) | 

trl rid (.hr- 1r.7, Jr.- .:l 2,?3 d (J\ / rr.a /r 

rr 

CH 

ol 

l.l?ap) ._,_l 

7t2 CH 

62.1 

CH ].rtl dd (Jn4-,,t, Jr\ A. L7) 

3-9, (o€t p), 3rl (orsE) 

CH 

r.xcbngquc ir a.h @lud. 

'Raodcd al 100 MHz in CDTOD. 

h.@rd.d .t 500 Mflz ir CDTOD. 

a9 

|

3.12.2 

4.12,2.1 

Krown Col3liluera! 

N-ForuyL@mh.07) 

conpound 17 ws isolated ftun lietion FF5 (? d ofbc ernyl 

eeiate €xtr@t of rinxPota dlsPd by cFtinv€ @lum 

chmtutosBphy on silica g.l (5-lt% EloAc 

'n c6HD) 

(Expqin nral, sectionJ.2.3.4.6, Pasel3l). Its HREI-MS 

showed lhe M' at ,r/t 293.1047, @rcsPonding lo thc fomula 

c,rH,JNor (calcd 291.1052). nt Uv sp4trM showcd absrption bdds a1313,274 dd 

235 DrD, indcltiig a conjurd.d dtrdc q.tch. Th. lR sPelrun tnosd sffichinS 

nEqkmis .1 1565-1425 (mturic ri4), .nd 1655 hr (mi& @bo!vl) 

compoud l7 @ id.Dtified s . hi{e of t (ExFriborrl, sedon'1 2.1.4 8.1, Page 

112) ad Z (ExFnlMt l, S€1id-3:.3.4.E2, P!8*l3l) 

obp€rison with th. Eponql d.h lP&hrly, 

'soEd 

{ 

l7 

of lv-fmt@Ei@ bv 

P., d dl, l92l (Fi8 3 2-2) In lhe |H_NMR 

sp€ru! rwo sin8l€b !r, 8.1? .nd 8.24 *G si8ftd to c-12 fodvl pbloft of lh. , 

md Z isone6, Bpetively. Tw doubl.G at d 6,09 (IH, d, JF= 0 5 Hz), and 5.% 0H,4 

Js.= 1.5 Hz) w€e dtiSrl.d 1o O-CHrO mdnytne prcios of t isBq *hile 3igntls at d 

6.07 (lH, d,4.= 0.6 l{z), 5.95 (lH, d, Jrn= 0.6 Hz) w€t for z isomer' Th€ ov€rlap of 

the lore p6ir of dllogen Mdr thc fodyl goup (CHO) Esulted in m.quilibrim bixtE 

oftz,6 shoM in Fis. 3.2.2. Th. TTC.NMR sperum of @npoud u al$ shoued 1wo 

str of si$.ls du€ 10 d/Z ism{izliiolr which w in &@rdn€c ro Fported dala 

lPacnary, P., el dl. 19921. Ik DPPH radical $av.nging lctiviiy hd alr€ady ben eporied 

ii lhe lilennE [C!vin, A., ,. a/., 1998], ehilc ii wE foud lo b€ non{ylobnc agaiNl 

botn nomal (3T3) sd cdd (PC-3) &ll lincs duinB th. cffit sudy (Chaplr4, Psse 

145).

t 

;y" 

FiS.3l,: tZ iffii.lion in @Fuin rt. 

t.t2,2,2 N-Fonyld.hydtudon.ln (lE) 

Conpoud 18 ws obtained iioh li4tion Fts5 (7 g) of the 

.lhyl Gtlte €xtad oI T,,o&ota .filpt by Epelilive collm 

ctrodDtosErhy on siti6 gel (5-1570 EiOAc in ,{ihd, 

dong with @npoud 17 (ExFri|@Ll, Seli@-1.2.1,4,9, 

PaeerlS)- fts EREI-MS slo*td tt ld tt n/.29L0a92" 

@RsFtrding to lbe fomult CuIltNOr (cdcd 291-089t Tne try s!6drum showed 

llorptio! b6nds ar 156, 330 ad 2E8 @, onglordiDs 10 @dueated mmaric rinct IE 

IR sp€trm showed ab$rption sl 16?4 cn_\CO} 

Tte rH-NNe speclrum of @mFoud lE (Expdime al, ?ag€'l3l) sbowed tloMfield 

sisrul ar , 7.22 (l H, s, H-7), insLad of signsk al , 4,58 (H-6a-. dd, Jtu r-= 

( 

14 5 Ha J6-, 

tut 4.2 rtz), 3.14 (H-7 s, d4, J1a1q= 14 5 H1 h\6= 14 5 llz)' 2.81 (H_7q, dd, Jaq r-= 

14.5 Hz; h4 tu- 4.2 ]jz) ir chpoud l7 doc to elidiMdon of rL noldule atd 

fomtiotr of a doubl. t@d b.r*@ C{. and C-?. ln tn. 'rc-Nl"R 

.pp6Fd ar , 126-8 ard l1 1.4 !d lw sigr.d io C{a !d C-7, repeliv.rv 

spelrtrb, tbc si8n 13 

Conpoud 18 rc idendncd d th. lnoM lr'-foDyldchy

J.IJ,2J rv-rodtbomucif.ri!.09) 

Compoud 19 w4 holat d froh fraLion Fr1 14 8) ot Lhe 

.I\!l zIf,att .xr!*r of Tlnotpqa ditr'o by cpctitive @llm 

clNnErography on silio s.l ll-t('6 &!rm ir GHu) 

rExFiD€nLl, Sdion.l2.J.t.0, Pagell4). Thc HREI MS 

showed the M' at r'lz 309. t 36 t, @mpondinS to 1hc fomda 

cDHl,Nor (c.lcd 109.1365). 'IrE W sFctun sho*ol bands at 3t0' 212 aA 222 nm, 

indi€ting a milert d mbatic sysltu. Thc lR sDeLn showcd absrPtio6 ar l59G 

l40O (mbdic ri!g) sd 1660 d ' (C=o). 

The 'H-NMR spdtm ofconpomd r9 (Expdimcnt l, Paeel35) showd tso si4lell al 

i 3.65 O-oM€) and 3.88 (24M€), @h ini.sFting fd tbc plolont, @ruponding !o lle 

mlloxy gblps, Tlr. sign ls ar , 4,49 (H{.r, dd. J,q rs= 14 0 Hz, J6. 7{= 'l-0 Hz), 3.1 I 

(H'7-, ttd, ,& ra= l4-0 Ha ./ra6= 14.0 ltz), 2.90 (H-?e, d4 J?4 ti= 14 0 Ha .Ita 6= 

4.0 Hz) ed 8.38 GOCHO, t, w€E Nigned b C_64, c-? dd C_12 prorotu, tespeclrv€lv 

of, i$ber ad d 4.92 (H-641, tll, Je( 7d= I 3.6 Hz, Joa ra= 4.2 Hz),218 (H'1-' d4 La 

k= tlt sa hae= 13.6 rtz), 3.ll (H-7e, dd, J'4'-- ll.6 Ha J4e= 4.2 Hz) $d 

8.24 ({CriO, s), aw Nig!.d to th. poroa of thc Z i$dn. 

Two ditredt scis of siSrils .lso .pF@d for .a.h 6bon of , ad z iem6 in th. rrc_ 

NMR speclrM of onPoud l9 (Expeircnlal, Pagel34l36), ex@pi for two singlets 

Geh for trc cdnons) at , 60-0 O-oMe), t6.0 (2-OM€) fd th. two tuthoxv sreups. 

On th€ hosis of this sletat dala @mpoud 19 *6 id€dtified a lbc tmm ll/_ 

fotuylnonwifqine, p'€viosty ierat€d iion I c/,rpa P&haly. 

P., er ar', l92l l$ eri- 

oxid&t md lip.philic etivili$ have b@n r.poned in th€ lit ElN icavin, A, ?r al,

l99Sl, wn @ iG clyotoricny ald itmbmoduldory etiviriG d cFn€d bv B for lhe 

nElirc (ChE 4-4, P!gel4s) 

t.122.4 N-Deu.drvt'N-lonvld.bvdtulomucd'rue(t0) 

Conpound 20 ws i$lar.d filn tt!.tion FFt 17 8r of thc 

elhyl elai. drr&t of ltost ts rlqa bv tp.fiiv' @l!m 

chnnarogdpby on silio gel t3-loq. .lstr ii Cdri., 

(ExFdn6tal, Setion-3 2-3 5.1, Pagel36) The HREI'MS 

sho*d ih. Ili at ttlz 30? 1205. coraPondits to dt fodula 

CdlrNOt (calcd 3o?.l2os) T!. Uv sP.din showd bands at 167 348 and 317 n'b' 

i.di€rins ! mjueat d enaric svs&n The IR spdmn sho*€d sEebhi'8 band at l6E0 

cn ' (c=o). 

Th. |H-NMR sp@d@ of @npouid 20 (E)(Fincdd, Pagc'l36) slFwed lle doMfi'ld 

siglal.td ?,12 (lH,s, H-?) instadof sigsLal'4'19(H{t'" 

rq- 4.0 nz), 3.1 I (H_7-' d4 '/'a ta= 14 0 Ha J?a 

dd' Jdtt= 140 H4J6r 

''= | 4'o Hz)' and 2'90 (H'7q' dd' Jta 

rr= 14 0 Hz Jt.q 6.= 4-o gz) h omFud t9' due 10 rh' pret'ne of ! doublc hond 

betw€cn C-6a and C_7 Th. C- I I ptoton appeded 6 donhle doublet al 

' ' 9'59 (l H' Jr I 

D= s 9 Ha Jrl,e= 3J rL) A o@ proion sinel't at 

' 8 88 B ssigned to 1hc C-12 prclon 

of lhe fomyl group. PretoN of ib! tso n thoxv goup6 app€lcd sl 3 91 dd 4 03' 

EsFcriv.ly- h th. rrc_NMR spetrM, th' sigD'b apFting al 

NigD.d !o C{! ed C'?, ttsT@livclY 

Cobpoed 20 *d identifi.d 

fomyld€hydrorcmuciferine, dli.r 

198?1. 

' 

' 

1283 and I 12 l w're 

s th. krom conpoud, ivdenelhyhv- 

i$lat d frem S,,ot r, .ari,r [Nozka T ' 

a ar''

3.1.2.2,5 M.s!ododrc(21) 

compound 2l w ohained lron Bua2c (230 ms) of fie bulMlic 

exFer of thc pl6i by uing Gyclilg HPLC (L'80' l:r 

HroM.O$ (ExFihent l, S@iioo-1.2.35,2, Pasc-137) hs 

HRFAB-MS (-v€) show.d rh. [M - Hf at "1/z 34t t6t9' 

@ft3poDdirsb tbc fomL C,ltxNO. (6lcd 14t.1622). Th. W 

sp6trum shosEd absorplioN at 330, 276 ed 270 M, indiolinS rhe 

pllsm. of a @njusd.d enalic aYslm. 

Th€ |H-NMR sp@trD ofanDoud 2l (Exp{ime a1, PEgc'llD snowd fou sin3lels at 

6 3.E0,3.79,3.31 utd2.E2. @h ilt8lalitrg fot thd prclo6 vnicL w. asiSled !o dt 

lwo m.thoxy (c-2 &d cno) ed th. ts! tuthyk (2-\M.: 4d l-NM.)' Esledvdv 

'IrE c-s &

150.2 indicslcd lhe pt*n@ of Otl srcuF, Gp.ciiv€lv. Conpoud:r wd foud !o be 

idmrical to rhe rcponcd tBgDflorine, sli.r i$lded non Ckfunpelot Alabnino 

lBarbo*-Filho. J. M, €, di., l97l ll m Epqt d to be norcvtotoxic rgdn$ a wid€ tuee 

of ell tin6 [Mi!, 

Y. D., el. a1., 2006]. 

3.lJ Tyra'nire atrd Othcr Afk ldd.froa Tinoqoft cft?a 

A nubd of ty@irc.ll loi& hlvc.le b€n ielaLd frod tieqo.. ctdPa, duin3 tn€ 

pEsl '.v*deatioo, 

3.13.1 

3.13.t.1 

Thce includ. tw tt?dirc all loi& 22-t3 dd a nuclosidc 2l' 

Knoivn Con{ilr.tra 

Crnpoud 22 !d obtained ftom ihe edYl 

@lale exlr&t ot I ct sra (ExFrnndtll, 

setionJ.2,l.5.3, P.gc'138). lts Uv sretm 

show€d lh. aberption ndim .r 30s, 29 snd 225 d, indi@tive of a conjugated 

dna{c nDcdonality, The IR speltum showcd btoad.bstptiotr bon& ar 3620 ed 1640 

cmr de io the Otl ed qFmetulted di

signars for rwo doubr€ doubters ar 6 6 67 (J!R ,2te 8 6Hz) u41 2? (.I* :r- &6 Hz)' d* 

to ,r,ro{@plbg of C-3'/C-5' eirh C-21C4,' t .l ofc-2rc{' virh C-3rc-5', E3p@tiYelv- 

Thc bndd-bald "c-tlt "petra 

(ExpniE)dLl, se.lionl-2 5 7, PagelSl) thoqed 

sigrals fd l7 6tds, iftludiig fou quorqD.ry (Cn, C4, C_ l md C'4 )' ten dcthirc (C' 

2, CJ, c-5, C{, c-2', C-l', cJ', c'6, C-7' ad C'8), two mcthvl€& (C-7 ad C_8) ad d 

dide carbonyl c&r,on (rc 169 2) 

Cohpould 22 shov&d sinild sFctlrt darr s rh@ of p.p@iie, Epon d .!lid fm 

FMtua indi.a l{tltw-Rttutu, et dl . t942]'. 

3.lj.l: ,V-I,@-t rnroyl.Yroilc (2!) 

Cmpound 23 s isbr.d tom lh. dhYl 

dciaL.xtz.t of t .ttuPa by uilg silica g€l 

@llM chrcDdogBphy (ErFrindt l, 

section-3.2.3.5.4. Pa8.-138) Ihe Uv sP€dtm showed .bealion msina 't 317' 293 

dd 2S5 nn, irdi.aling th. Dllsc of d arenDtic fitudoDtlitv- ThG IR s!6LuD slbsed 

brcad absoptio! bdds .t 32oo 6tl 1655 cn-r,de lo OH ed d'Fwtdat'd mid€ 

clrbonyt 6etio$liti.3, BFctivcly fts HR.EI_MS showd Nf ai ttlz ll3ll09' 

corcspontlins !o lhe fo@d! CtrHreNOa (calcd 3l3l3l4)' wiih ten double bo'd 

.quivale . in lle noleule. 

TrErH- andriC-NMR sp€FM of@6Fu 23 (Expdimctrt l S.ction'3 2 1 5 4' Pas'' 

Il9) sho*e{t stu rat f.ai@ s clos b lhoe of @mpolnd 22,.xePi 1har onc me$oxv 

sroup rppeacd al dH 3.s9 (& 55.6) s a singlct, ad ! qoddDart ebon @MLd at 

'c 

147.8 insi€ad of one emlti. sienll ai ,H 6.67 (rc l3O 7) in conPowd 12 Thc posilion of 

lhc m.lhoxy 8rcup E ddmincd o! lb. bsis of th. @@latiotr of th' relhoxv potons 

esonaiing at,3.89 withC-l (147 8). 

r-tiY'

-Irie conDouid 23 I idendlicd s rh. tnoM ,V_l.da-fetulovl tv@inc bv €onpeien of 

$@l''l dara wiih lh. €pon d data lFltuda N ' 

.t a/, l9$] Ir {a rcponcd to bc 

rcncfobri..sA!s a wid.6nge ofc€ll lid [MiA Y D,'t 2006l lts 6ti4xidanl 

'l ' 

md lipopnilc piolertid re rcpon€d in ttE lit Btft lcsvia A ' ,r a/ , 1998] 

3.1.3.1.3 M.lbyl-3,4-dibydrctybeMd.(24) 

ws islated froD th. .thyl &.1a& qtlct of I crqu 

S6tion-1.2.1.5.5, Pagc-ll9). l$ EI-MS tnd ERFAEMS 

rbe M| ar d,4 168.04l?, @n sponding lo th. fomul. 

168.0423), vifi five doubl. bo equivalmts il the 

rtu rH-NMR spetiuh of @nFud 24 (Expaihetr.l, Paeel4o) shoqld t*e dowtr'ld 

doublds al d ?.53 0H,.46= 1.9 Hz) ald 6 90 (4.6= 8i rL) wE d* to H_2 

'nd H_5' 

FsFcriv€ly, A rloublc doubl.t ai 67 63 (rH, J6,- 81HaJar= I 9 Hz) wd 4sierEd 10 

th. C'6 prelo.- A sinslet .t , 3 91 orD *6 d@ b in prctoc of n'lhoxv 6rr' Two 

hyrdmxy FotoN ale apFad a,l , 5 2 @d 3 5 in @nPo6d 24 Thc TTC-NMR (BB 

&@upled 4d DEIT) sFclrud of.ompound 24 lhov.d siSnats for 8 carboN Tke' 

qulcnary csboru lPp.atd.i, I2l.l (C-l), 146.4 (C-3) @d 1492 (c4) Signals 

tsnrilg al , I 12.4 I t4-0 dd l24 l, 9w sig&d !o the @Mtic tuthic @tos (C- 

2, C-3 &d C-6, esp4rivety). SiC ls at , 55 6 &d 168 2 {.re 6$8red lo l!€ esrcr 

merhoxy 4d 6Er cdbonyl, t!6p€clicly, 

Conpoud 24 showed sinitr sp@tal data qilh thn of E€dyfl,4-dihydmxvbcmal'. 

@li.r Eponc

3.1.3.1.4 Cylidi!.(25) 

Conpoutrd 25 M lelar.d freF rhe but mlic Gtlr&! of lh. Pldtt (ExFri|md' S€tion_ 

3.2.1.5.6 P.86r40). Its IiRFAB-MS C!c) ihowd rhc IM ' lrt- ^ n/t 242085E 

cor$odins lo |he fomula CrgEN3Oi (c5lcd 242 0855), indiotins 5 doubl. bond 

cquivalars in dE @lede. 

Thc |H-NMR sFctun of @tnpoud x (Expqimental, Pagen 4l) 

slFwd sisnsb cb!rurqisric of a qtGine b.s {D.rebo, A, er 

ai., 200I. lt showd tso doubl.te al r 5.6E (lH,4.6= 6.0 Hz, tt- 

t. and ?.98 (lH, J6 5= 6.0 H2. H{) due to C_5 dd c-6 Pbba 

Th. |H-NMR speEub shoecd sierbls for tlt dcoxFho* sug& 

with cht@t rislic./valEs. 

Ttc frGNrlR siglds sho*td 3igtttb { 6 622,863,7l.l' 75.? !trd 90 7. whrch 94 

6sis!.d ro 6boE deciar.d b tb€ doxltibo6e sugd (C-5', C4" C'3', C'2' ad C't'' 

rs!€.tively). TIE ']C-NMR sp@tru .l$ slDwd si8$ls for C{' C'5, C4 d\n C:2 

^ 6 

142.7. 192.6,1(6,l ald t52.4, Espeliv.lt, Cobpoud 25 6 idenliflcd I crtidine' 

i.eorr.d tom $c ldvcs of Mct peppt (Capshum atut@r ID*.bo, A., et al ' 2007 J 

3.1,4 

3.1.4.1 

3.l.a.l.l 

Ph.lonc rd Triterpen.. 

KDown Comtituents 

SF"s" (2.6) 

']on 

n"oqotu oirye 

conioud 26 ws i$lai.d nom th. blilelic.xn! t ofth. pldt (ExFircnt l setion- 

1.2.3-5.?, Paecl4l). lts flREI-MS shostd !|. rrf ar,,4 l?4 1J62, @Blottdiig b $c 

nol.culd fonula c nHrO-H! (calcd 174.157). 

93

th. IH-NMR sFciim of @npound 2? shovld ! doMfield brcad singlet at d 674 

odlsronding lo th. C-2 add C{' Nmlic Ptolos. A d,oubLr of dplct .l , 6 30 0 H Jr' 

,= 15.9 Hz,J2.,= 5.5 Hz) &d a doubler at 6.50 (J:.r= 15 9 

Hz) vw d@ to C-2 ed C-l proto.t BFcliv.ly The C'l 

mdhyle.c prcloN apFatd 3 a doublel at , 4 22 (J',,- 6J 

nz} A 5H sinstet at r 3-E4 M Nigred b CJ' aId C-5 

codpould 26 m i&ntiEed s s kloM @EPould sttioeilq PEvioulv 

Compould 2? 6 isold.d &om th. bqtamlic .ft&r of th. 

plad (Expdin€ntal, Setion-3.2.3.5.8, Pa8._142) Ir5 

HREI-MS sbo$cd dE lvl' ar r/z 2?0.0522, @clondirg 

10 thc c6HrcoJ (cdcd 270.052E). 

i$lal€d fbn 

Sk ea.hMi6n,.atlEt,tnsof @npdi$nof AeEatdatawihthdof l[cEpolrcd 

dala [Jin, 

c., .l ur, 1999]. 

3.1.4.1.2 1?-Dt[tdrc!y-2-(4-nydmryPboylF.r_bcMDtr.n'4oft (27) 

The |H-NMR sFcriM of @nFurd 2? dbpl.ycd rio doubLts itr de mntric Egion at d 

6.44 (lH, J6. s= 2.0 Hz) md 6.1 (lH,.rr6=20Hz)du.toth€c4and c_8 Ploto6' 

Esp€criv.ly. A singLt a1 , 6.58 (l H) @ NigEd to th€ C'2 proton T*o 2H donblas at , 

?.E3 (2H, J1'61 

'D= E.? Hz) &d 6.9 t (2H, $r ?d) *ft Nisncd to H_2 /H6' and H'1111_5'' 

Ihc siructue of compoud 2? e $.Efo€ deduced N 5,7-dihvdtoxv_21+ 

hyihoxt?hoyry4tt-l-beMFru4-@, E?ort d in lhe lir.Ftw [apoldini' M.' .r ar, 

20041. 

o

J.l.a.l3 Cy.h.!€L!ol(2t) 

Conlound 28 @ isotaLd fbn tlE ,-he*e a|la.t of I .fltPa bv 6ing sili€ s€l 

@llN clNmtogapby (ErFi@lal, Satio!-3.2 3-5,9' Pagel43)- l13 HRg-Ms 

shor€d ih. M' !t ,,4 426.3863, oBPoding 1o rhc fodul! crollso (cdcd 426 3E62). 

T1'" 'H- ed "C-NMR sF.ta of ompood 28 (ExFdndtal' r.s€143) slDrtd 

ch@teiisric sisals for cyclosl@type of trit DeB An orv!.sr€d C-3 nclhine 

siSnal app.dcd at rH 3,19 (dc 76.5), 5loh8 {ith 3iSnals for six dethvl eloups al , l7 ?, 

18.3, 22,0, 2f-8, l9,l .!td 14.3 dre ro C.lE, C'21, C'26' C21. c-2a ad C'29 

E$drircly. IrE C-19 mthyl* Prctoot of cycloprcpon. lpPatld it lhc doMficld 

Egion of thc sp€trM d doubleb ar dx 0.36 ed 0 12 (ieq ra- 3.0 Hz' 6c27 2). TIE C'30 

olefinic prctos, dis"teycd a doubl.t al r{ 4.64 (40@- I5.0 Hz) (dc 105.D on rh. b6ir 

of ths. ddr, S. slructN of .@poud 2a vg dcdw.d to h. th. tmM cvcl€F3lml' 

pEviouly ielaled nom fi'orpotd .riP' lKotrgklthip, N., er at, 2002]. ft h knom for iLs 

wdia€ ooti&tilrty, md hep.iopolectiv€. 

!.1.4.r.,1 !-GlDct!..pyn!6yv{il@l@1(29) 

conpoud 2t ws isotdted frcm th€ r-h€Mc €xt&i off,dPota.tsPo bv !sin8 silica 

s.l6tffi ctmoatogBptt(ExPdiDe .l,S€liotr-3.23.6.0,P.ge|4l).Th€rH-lrd rrc- 

100

NMR?.d. of ..ryt d 29 noEd cl@itdc {gob tu 34&Drhlnr'vavl' 

,dcd{it tt- ld-d.diafio r.vt .l!ld w.XE & D' t9621. 

101

CHAP:TER. 3 

E)GERIMENTAI

3.2.0 

3,2.1 

l,2.t,l 

3,2,1,2.1 

EXPERIMENTAL 

Gemrcl Erperinentrl Co[dlforg 

Anabticsl, HPLC or laboratory srade $lv.nts ed chcnicals w.e puchAed &om E. 

Merck, Fish6 Scicntifi. or Sip! Aldrich. 

Meltin8 poi s q.rc dclcroined on a Y.@o MP-S3 .p!.6r8. Oplical oialio$ l'* 

n6Ed on a diSibl poldin &l JASCO DIP-360 in D.rh"ml or chloofom 

!.2.12.2 Spdltu(opkTdhriqu6 

uv sFclla wrc @ordcd o. a ShisEd^ UV240 sFclrophotonet r in McOH solutions 

dd ptEst€d d L-, M (los .), ard IR s!6t! v@ eorded s KBr die3 or a JASCo 

A-102 {.6ophotomct r ad pMr.d h c'n-'. lD 'H-NMR spccrii wd @rd€d on 

Brula AG3oo, AM4oo !!d Al,|o

3.2.1.2J 

Collm chnbltogbpny vs Frfom.d on silio 8el (E MercL 'O40 ed 200400 Fn 

mesh). Puity of the smpl€s w che.k€d on prco.1':d sili€ g€l TLc (GF 254). Diaion 

HP-20 (Milsubbhi Che6- lnd., Totyo,.lape), ODS C-18 (61-212 Fm. Wai

fou @jor n&don\ Fh€lo. (60.31 s), el[yl @r.r. (69.43 g), ,-buta.ol (?2.61 s) .nd 

*dtd (81 .65 e) 

(SchmF3.?, P$.'106)- 

J.2J.l LoLlion orP!rc Coudrrds IEE tn. Elbyl aetrt Elttut 

Ilrc eihyl MllL .xtta.t ws subjc.t d 10 @luDn cl&natography (silid gel, 200400 pm 

ftsh) a.d eluL.d vil[ sradida of Fh.e.: @rorc (95:5) .nd Fbermr dnyl &.1a1. 

(90:10, 80:20. 70130) od fitr lly sasbed wih eftyl @tat! (l00er). A tord or find 

netio$ (FFl lo Frl5) \rw colLcted (Sch.c3.?, P.gc-106). orr aurlhd rep.litiv. 

@llm chMEroslpLy of fi!.rior IF5 (7 8), {!E krou lporphift .lkdoids, /v- 

fomyleomim (17).,V.fomyLlehydro@ldft (18) rid lr'.d.n€lhyrlr'- 

fonytdchy

Lol.rio! ol Pon constit!.llt fmd t-But{trol Ertr.cl 

Th. bd@lic dt a.l (72.61 g) of th. pl&t w l@d€d on a D1.id HP _20 6in @ll|m 

dd clur.d *irh | ory. $!i.r, RElq: n tbeol (3:l), $dq: neitt@l (2: l), u.r€. turhsol 

(lrl), mlec m.thml (l:2), ad 6n ly with 100v. m.rhdol to vicld six ftncions. 

TIE 2d (Frb-2, ?.3 s) ed 46 (F$4, ll.l g) Aedos ton gP-20 @ltm w* @mb,ned 

dd funid ieiioalcd by oDs itrb sn iub-ftaclioN (Bu-l to Bur6) DE $b-fi@liois 

Bu-2 to Bu-6 wre p.ssd thrcugh sephad.x LH-20 @lum again 10 obt in 3_5 sub' 

t'&tios. The @irina fE lios 6m HP-20 @lu@ (Frh-3, Fd5 ald !rM) lw .ls 

subjet d to lhe almtivc qGF Dh4 @ll|m cbbnbiosnthy or oDs (RP-t8) 

follow.d by Sephader LH-20 10 get li&tios fot fttthd puifi..1ion by uing @ycling 

HPLC (Sc[oc].8, P.€!-107). 

All suFFa.dos lhs obLi!.d w@ puificd by Bing @ycling HPt C, LC-908 oo ennd 

!-80 ot Gs-320 colMns eirh wrer-methaol (l:l) dd n€lhoola clual lo obt in $e 

hos compour&, booFtoside F (rt, crridire (25), bohFrosid. C (ll) (S.heme-1.E, 

P4el0?), srrinsi! (26), boEFrosid. D (13), tr stuflonft el), b@p.tosi& B (10) 

(Schmc3.9, Pace-l0E), boDFtoside c 02) (S.h.@3.1.0, P.gFl09) dd honp.tosidc 

A (la) (s.hd*-3.?, 3.1 .1 dd 3- 1.2, Pag€s 106, l l0 dd l l l). All thc re* @mpou& 2- 

9 .nd 16 re isohbd Aom th. bl^@li. .xg*r of Ti6pora .tlsq,.xc€p1 for rhe Gw 

@npo@d l, dich a obranEd fiob thc.lhyl @t t qlr&r ofrhc pbnt. 

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:

S.[cne!.|rr Isolation of compounds 6, 13 and l{ from ltdPora t/irPz 

!JJ3 tsbrio. ofPon Coudr{..o fid tr-Bdu. Enn t of I .dry! 

The h.xrne €ltE i (60.3 I d of th. pldr vs lielion t€d into fiftv fi*rioB Gu 

ro H'50) 

by col@ cb@loSr.phy on 3ili.a, e{tin8 ftoo I007o hcxm with tlE gEdicnt 

in.tle orcNoofom (l-10,6) Cycl@uc.l@l (21) vs obt incd lion fr..tio4 H_13 ro 

H-17 (60 cEcL in ,46HD) 3 a whit elid (Schcc3.1.3) 

t-tT 

s.LdF3J3; Isolttior of cyclocu@lcnol (2t) from thc hde qtld of r mbpd 

lll

3.FJ.r tuDpblolE (l) 

IUPAC: Metnyl (2x,?S,8.tj.8-(2s)-2{3jdihvdroxv'2.5_din thoxvictlhvtlG3_ 

nlm/!2-hydex'€thyll-2jdinethyl- lo{xel l{blncvclol? 2. t.0r'ldod4_3_.c3' 

The .thyl celalc qt@t (69,43 g) ol TitusPora .rispo v6 subj@Ld 10 @lum 

chrtmtosraphy on 3ilics 8€l by Bins &ctoff/r-hcx.de (510'lo) &d cilvl &elai'/ h 

htu (15{0v") to .flottl nnm fi!.tios (Frl to FFl5) FtudoN Fr8 @d IF9 on 

frllls @llm chrendognpny d silio scl ( 1094 .a[vl 4ela&) vi.ldcd @mpoud I d a 

whi& slid (2.0 ng, 1.2 x lor% yi.ld), {hich 6 cb@reii.d 4 Mphiol E (l) 

{Schene3.7, 

P.M!t ge ti.ld: 

Pdg& 106). 

1.2 x l0'r 

Sirft: rvhrre cr'6t!k frcE .rhyl !.elde-hc;4 

M, o,t 206-207 'c 

IdlD': 

+2?.5'(a 0.04, CHCb) 

rR 0(Er) v- m_r: l55l, 1505, 3l9l (olD; | 745, l70l (c{) 

UV (McOH) r.* M (lo8 s): 242 (2.32); r,,h m 0og €): 23a (1.23), 349 ( 1.26) 

flREStMS (+vc) t/t: 471 .23 12

t-Hydotybonpct6irlG c o) 

IUPAC, (2x,5n,6x,8x,9s,10S,l2t_15,15'E!oxv'2-hv&oxv{l 5, l6€roxv-2-hvdrxv{'(/-r'-glMpvl@3vlFleroda- 

3,11( l6),14-ttiol ?,12-olid-18'oic eid nethvl €ster (2) 

P.ft.lrts. yicld: 2.4 x l0_' 

sr.rc Colorls sumy elid frem mtbml 

IdlD": 

-22.7' (c 0.I ?, CErOH) 

IR (lG.) vd c'n:': l4o9 (o'H); l?09, l6?0 (C=o)i 150+1438 (tum tins) 

(rv (McoH) L- nin (loe r): 223 0 94), 2l? (5.17); Lft rn (los 0): 218 (3-05)' 212 

(4-99r, t92 (446) 

SR.ESIMS (*.) ,/,r 553 2215 (C,H!Oo+H' calcd 551-2280) 

lll

FA&MSGE) t /r:551[M - 4f 

EI-MS (?O ev) '/' (%): 389 (13),373 l3T),351 (20), i4r (27),296 (8), 235 6), 205 (31), 

2Or {20), 14? (25), r 19 (70), 115 0 5), lO? (24), 103 Ol), 97 (29J,9s (66),94 (64J,93 

(21),9r {68),8l 000),6l 

(53),60(60),55 (62). 

rE- .nd TTGNMR: se TabL-1.2 (s@rlon-1. L l I 2, h8.-42) 

3r3J3 lbsrbpdld. A (3) 

IUPAC, (2X,51?,6X,8S,9S,IOS,l2,t!15,i 6-E!o*y_2-hydrcxv'6" {pDglucopvreosvl_ 

(l -6){-D-xylopr@@}{Lroda-3,t3(lO,l4.l'i@U,12-olid-lE{ic4idb.thvl 6Lr' 

'ft. but&blic €xtet (?2.61 g) M lo6ded onio ! Diaion tlP -20 Bin @lu@ ud €lltcd 

wnh walq ed dclhdol in gzdi.nl hgM (2il00e/0 to @llal six sub'f6.tios (Frb'l 

!o 6). lm or tlEm (F.ts2= ?-3 8 ed rr* l3.l s) l@ onbin.d .!d tutlEr 

f@tioBld by oDS @lum inro six sub-nedoE (Bu'l to 6) ne sub-f@rioN (Bu"l 

&d B!4) (2.1 I ed 3,5 g, tr94tircly) wF @dbincd rog.lh€r dd pe$.d lhrcuSlt a 

Sephlda\ Ltr-20 @lmn .gein 10 obrlh th€ $h-n&ioN (Bwla, Blcl dd Bslc) 

'nF rhid fraction (Bel c, L2 s). €lut d with 10P,6 M!oH, B th.n p€nition d aeai. ino 

6r $ts&erioB (M-l !o M-3) otr sili€ s.l 

by uins ed'@l i! c mfm (5'15%) 

(schd.-3.1.1, Pag.-llo). F@don M.l (781 ns,5% M€oH in CHCIs) wd fudn€r 

pui[.

ldlD'r -35-d (c 0.056, cHroH) 

IR (KBr) '* d ': 3420 (o-rDi 1717, | 63? (C-o); 150?'l4'l0 (furu nna) 

w (MeoD r* m (los s): 22a (1.t5), 214 (5.16)' 209 (s l6)i xd m (log 

(2-54), 216 (4.{0), 210 (4. | 2), 205 (1 84) 

HRESI-MS (+r) r/z: 685.2?01 (qrH{O|6+H, calcd 685 2708) 

FAIMS Crc) ,'r: 683 lM _ Hf 

')i 350 

Er-MS (?0 ev),,/, (%)r 3?l (3), l4l (3), 125 (l),261 (2),205 (6)' 147 02)' 133 (64)' 

1le ( lo0), 95 09), 94 (24), 9l (5S), s I (29), ?l (61), 6l 06), 60 (15)' 59 (9), 55 (30)' 

'lI-.od ''oNMR: see Tablej.3 (s.ciion"3 I l.l I' Paga48) 

3J33.4 Tbc]lDo.ide a(0 

llJPAC. (5i,51,8s,9{,loi,l2.t}l5,lcE oxv-2{xc6d-D-gl@ptre'gvl){l'rod!- 

l,l3(16),1+k cnl7,12_olid- l8_oic &id n€rhvl esl€r' 

A fracion Frb-3 (5 7 g) too (h. bursmlic dit&lts loT t'd onto s oDS s'6c ph$' 

sllM and.lut d w h lO0% ncthaol, *t r_nethlnol (l:l) md l00e/o watet to @nec1 

lhc sub't@liod (F.b3-l to Frb3_l) Fftl'2 s tunh* r'actionated ino |hF sub_ 

&acrioB (Fql. FlF2b &d F+3c) @ polvdide @lum bv uing ncii@l iD 

c|noofod s .led (lOO94 CHClr, 5% M.OH od 1096 MGOH' 6peliv'lv) Tw si- 

p@ t&tio6 (Faltsl .ttd FD3F2) s@ obr'i!'d fi@ dv'liry tlPt'c (LE0' l:l 

Hro/MeOH, 4 5 nvnin) sub-nedon FrPlb-2 (ll mg) *her tubjdEd ro @vcliog 

HPLC (CS-320, loe/o MeOH) sfiord..t a mw @npoud 

' (3 2 ms' 2 0 x loi% vicld' 

TR= 44 min) (s.h.me3 l 0, P.gelo9), whicn wd i&din?d d (5x'6x'8s'9x'l0i'l2t)- 

t5,16€poxy-2{xo6'fPDglu@ptrmsvt){l'oda-3,11(16)'14_lticn_17'l2did_18{ic 

ll5

Perc.nlig. tield: 

2.0 r l0'r 

Sttt.: Colorless gll@y solid fom meth4ol 

Idloz': '33.l'(.0.18, CHrorD 

IR (KBt v.- cD-': 3a26 (GrD; I ?25, 16?3 (C{); 1504.1 439 (dmatic ritg) 

trv NeoH) l-- n (los '): 216 (4.55), 2ll (455); Lh m (loe s); 2!l (3 49)' 208 

(r.8D,199(3.83) 

rnEsrMs (+ve) ,r/2: 5512113 (Crll!Or+H, @lcd 55r '2123) 

FAFMS C!c) n/, 549 {M ' Hf 

EI-MS (70 cv) i/2 (%): 550 (2), 388 (9), 371 (2D, 356 02) 139 16)'291 

(4)'222 (t2) 

203 (16), 167 (21), 133 (39), 119 (2?), ll5 (16), l0? (22), 103 (12)' 97 (2E)' e5 (60)' e4 

000), 9r (21), 9l (55), Sl (S3), ?3 (5S)' 6l (36), 60 (58), 59 (31)' 55 (56)- 

!u- dd'tc-NMR, se T!blF3.4 (sel,oFl.l.l I d Page_s3) 

!:JJi TilaniPotidc c (t 

IUPACT (3x,4l.5l,6,tEi,gs,les l25)3.4,t5,lGDicpoxv5(,+lglMprtuosvr)' 

cl€oda-3,I3(l O,l +timr ?,l2did{ic &id ncrhvl 6Lr' 

!@tior FF2 (l.l s) aon a Scphartd Ls-20 ollm (tl,O/lvleoH(3:l) or dE but'nolrc 

qtr&t*s loadcdo o a L40 @lum of dvcling HPI'C (l: I rLOA,leOtl' 4 muni!) !o 

afrord a n w @mpoed 5 (2.9 m& l-s x loj% viql4 TR= 37 nin) (sch€@18' Pagc_ 

l0?), (3,R.4&5x,6S,8X,9.t,l0s,l25l3j,l5,l6diepoxv-6-(&D-gleopvtsosvl){l€oda- 

3,13(16),14-uien- 17,12{lid-18{ic mid methvl este. (O 

P.rcctrlrg.yicld: I 8 x l0_r 

Sl.tc Colorlds gl!@y $lid ftoD mclhaDl 

lt6

tdlD I'r +135.1./ (. 0.0?a, Cs3otD 

IR (KB.) r* d ': 3aa? (O-rD; l?l4, 1635 (C{); I508n 423 (@maric ri's) 

Uv @eorD xd. m (log.): 222 (4.35) 203 (5 55)i Lb m (los '): 2l? (4 34)' 199 

(4.52), l90 (4.56) 

ERESIMS (+vO t/z: 551-2255 (CrHroriH ctlcd 553 2280) 

FAEMS (-ve) r'lzi 551 [M 

- Hf 

Er]"1rs (10 eV /z (v,):3T o)34t Qr'323 Q)'2s5 Q''205 (6)' le4 000)' 16? 02)' 

lle06),l0? 0l),105 05), 97 (4)' 95 (1r, 94 09),93 (7) el (28)' El O9)' ?l (24) 6t 

00).60 08),59 

(9), 55 (13). 

'H- rnd'!GNMR. s@ T.bL'l 5 (s.ctio!-3 l l l'5, Pag'J9) 

3.2.3.3.6 li.ocd.Polide D (6) 

IUPAC: (5x,6x,8s,9x,10$,121)-l5,l64Doxv-2{xo{{''}etucopr@svl){l'oda_ 

3,1l(16),14-tieo-l ?,12_olid_18_ oic &id melhvl esrcr' 

sutsfr..iion Buc2 (1.3 g) &on tlF b aetic 'xtlct s ponitiotd i o ne$'nol (B{c2b' 

2.1 s) dnd laid soluble (B@2a,70 Fs) fi&hos Med6ol sluble fi*tion @ 

subjdcd ro siliq gcl @llM cbreodognph, to l$od fou suFftdtios bv uine 5-20% 

(MeoH in CHCI3) 6 Gl@t simild tu'nots (BE2b_12 to 15) rcE @inbincd on ft' 

bsis of TLC beh6viou dd subj€cted to Fcvcli4 HPLC (GS-320' loo'/' M'OH' 3 

mumitr) (Schc@3 1-2, ?asel l l) 1o obi'i a tuw @mFud 6 (4 1 n8' 2 6 x l0 !% 

yicld, TR= 54 mio), (5,1.6x,8s,9x,10s.12'tn5,l6{Poxv_2{rGqF}gl@pvMosvr)' 

cl€odal,l3(16),14_rien-17,12-olid'18{ic acid nefivl esi'r (6) 

Pddt g. Yi.ld: 

2.6 r l0 ) 

Shlc crlorlds gllmy $lid fion melhdol 

lt7

lalD': 

+260.Eo (. 0.0a6, CH3OH) 

tR (KBt '- m r: 3421 (o'H! I718, l6?4 (c=O); l50t 1437 (enatic riry) 

UV (M.OD r.-. @ (los €): 225 (3.80), 215 (4 38), 205 (5.26)i rd' m (los t): 218 

(3.86),215 (3.85), 204 (4.3t, 196 (4.5D 

SRESI-MS (+re) t/z: 551-21?l (c'H!odH, cdcd 5512123) 

FAFMS Cvc) n/z: 549 (M - Ef 

tH-.od'3C-NMR: se Table-3.6 (setion-3 1.| 1.6, Pa8e'64) 

3J33.7 ThotidcA(7) 

IUPAC: 0,l,4,t,tr,ss,9l,l0s,l2D'l5,leEPoxv-4{r-}slucop}1@3vl>clddt_ 

2,t3(16),l4rric!.1?(12),18(I)niollicl@d.'2,13( 16),14-tfl'nc_ 17(12)' 18(l )diollide 

PcraLg. yi.ld:2 ?x |0'r 

strL: Cotdlds gllmy $lid &om D.lh!tuI 

tclo': 

-Er.ocf (c 0 o+0, CH:Otl) 

rR (KBr) '- o ': l42O (o_Hl l75r , I ? 16 (C{)i l50tl lE4 (nr@ ntrg) 

Uv (M.OID I^ M {loe s); 220 (3 46)' 2r2 \482)' 208 (4E2); r'h m (loe c): 216 

(4-08), 209 (4.09), 20J (4.00), 200 (3.86) 

I|RESI-MS (+ve) t'lz: 521-20t3 (Cdlson+ll cdcd 5212017) 

lt8

FA&MS Cvc) ,,/r: 519 [M - tt]- 

EFMS (70 cV) r/t (%): 3 14 (r q,2a1 Q),252 Q\,zm (\,206 (39), | 6l (3 | ), 134 (41)' 

r2l (88), 119 06), 1ls O3), 108 (98), rO7 (39), l0l 02),I (21),95 (50), I (56),93 

(10), 9t (66), 8l 0 00), 73 (86), 6l (60), 60 (12), 5J (46). 

'H- -d "c-NM& se Tallc-1.? (senonJ.l .l.l.7, P.s.t) 

3.2.1J.E Bodp.rorid.I(E) 

IUPACT M.Uyl (2s,6s,6aX,9i,l0as,l0bs)_2{_luryl){-, }slncolvr4osvl_9_hvdroxv' 

64 | oHi6.Oy!4.xo1,4,6,6a,9,t0,10a,10b{lahy&c2tt_bc@tllistmn.@?- 

Trc $d-p@ tacdoB (!A2Gl ald f.p2e2) s!!E obl!i!.d ton @vcliry HPLC (L' 

80, l:l wl.FoerhaoD. rD2c-2 {? ns) yi.ldcd a pw ontoud 8 (3 ? E& 2l x l0_r% 

yi.ld, TR= 12 nin). wst ohain€d by $i4 ectlli4 ttPLC (GS_320 l0(P/0 MeOE' 4 

hunin). conpound s {s trivially 'ded s boBFloside I (Schde3 l 0, ?age_ 109) 

P.ttdt!8. yhld: 2.3 x l0 r 

Sr.i€: Coldtd gl)my slid ton m.lheol 

lolD 1': +l0.90 (c 0.06a, MeoH) 

tR(KBr)vdcsf rr 3430(GH) 1725, 1664(C=o) 

W(M.OH)l-m(los.):208(3.82Ildm(1o86): 198(166) 

rnEsLMs (+v.) ,/z: 5?3- l98o (CrnqOD+Na, c.lcd 573 1948) 

FAFMS {+s) ": 551 M + rll', 573 lM+Nrl', 3E9 IM' 1621" 3? I M- l80l' 

rrl-.nd DC-NMR: sE TabL-3.8 (sedion-] I I1.8'Pagc?2) 

ll9

323j.9 Bonp.r6ld. J (9) 

IUIAC! Mclbql (2s,6q6.&l0.S,l0hsl2

313.,1.0 

sub-6*tion Fry2 (900 ms) ftom polymidc colufu chrcmrogBphy (5% M.oH in 

CHCL) of thc buirslic drrd B nodly pufi.d by Byding HPLC (L-80, l:l 

H,O/MeOH, 3 ml,/min), Ih€ puifi€d conpoud l0 (834 dg TR= 38 nitr), M 

ch.futdizd s a kmM @mFuld bo6Fro6ide B, *lich B de obt{n d ndr 

fnction frpc2'2 (56 Ds) by s.l Fm.ation cluotulogBphy ot Myclirs HPLC (GsJ20) 

(Scb@6 3.9 ad 3. | .0, Pag*108-109). Th. @obio.d yicld of bq.gerci{b B (lo) fion 

$etmt ctiosM5t.2x lo'%yierd(883m8). 

Pe..c rg.ti.ld:55,2 x loa 

$.r.: Y.llowish gllmy $lid ton m.rhml 

lalD t. 15.?p (c 0. I OO, McOrD (Lit -lo./ {. 0.102, M.OH)) 

IR (KBO r* m ': l42O (Or0; | 716 (C{) 

Uv (MeOH) ,qE m (log e): 210 (3.44, 197 (5.s9) 

HRFAB-MS Cre) ,/,i 5s l.2129 GrHraOD.H, calcd 551.2134) 

Fâ-Ms tv.) n/r: 551 [M -H]- 

Er'Ms (70 cv),/z (%)r389 (5),373 (17),35? 0D,341 (14),296 (3),205 0s),203 (13), 

145(2r), l3l{30), I9(39),91 (56), 81 (80),60(r00),55(6D_ 

'I|-NMR (cDroD,300 MHz)dr2.2l (lH, orcda!. sna),2.02 (lH, ov.rlaA Hnb),4.51 

( I H, td, Jr r= 8.3 Ha .4 t- 3.E Ha H-2), 6.40 (l H, 4 Jr.1= 3.8 H4 H-3), 4.5? ( I H, bd, Jq 

F 2.6 rlz, H4),2.24 (lH, N.drp, tl-?a), 1,46 ( I H, l, Jrr rft= 13,0 Ez H-7bJ,2.21 OH, 

ovdla!, H-8),3.42 (lH, bi4 ia r= 9.6 nz, Hno),2.0E 0H,4'a 'r!= 14.0 Hz,4lah= 

6.1 Hz, H-l la), 1,98 0H, rlC, J|rr, rr= I4.0 Hz,..4rA Dq= ll.l H2, H-llb),5.53 (lH, dd, 

Jri4 r rr l l.l Hz, 4,a rk= 6.1 Hz, H- 12), 5.50 ( lH, 4 4{ tr= l.l liz, H-14), 7.50 ( l H, r 

I2l

ft.!x6= 1.6Hz, H-l5),?.58(ltls,H-I6), I 55(3t1,sMa|9),096(3H s,Mc20),l ?4 

(3H, s, co,Me), Oru: 4.4r (r H , d, Aa,n= 7.6 lt1 H'r),3 18 (l H, dd, J6 c 6't= I I 7 H2' 

Js,, s,= 2,t Hz, H"6a), 3.12 llll, dd, J6\6i= ll 7 Hz, Jq sn= 4 6 tlz' H_6'b). 3 20_1 34 

(aH, ov.rl.ppiry !ielEl). 

'rc-Nia (cDioD, roo r'trrz) 6:29.3 (c-lr, 64.6 lc"2), 140.1 (c-3), 140.1 (c_4), 42 8 

(c-5),80.05 (C{),2?.6 (C-n, 5r.5 (Ca). 38.2 (C-9),42.2 (Clo),46.2 (C_ll), ?19 (C- 

12), 126.0 (C-11), 109.8 (C-14), 145.04 (C-15), r4l.0 (C- 16), 178.4 (C-lr, 169-4 (C- ! 8), 

29j (C-r9),2J.1 (c-20lb s2-3 (COd4d, 106.3 (c-l ), 75.5 (C-2), n .1 (C-3\,1t.3 (C4), 

78.r (C-r), 62_4 (C-6). 

3.2.3.4.1 BonpotorideD p. re.lt (lo-Ac) 

Acciylaiion of 6 (100 mg) with Mic a$yd d€ (5 eL) in Pvidift 

(10 nL) al mn 

ieDpenlur vs @ied ou1 tly ov*-nighi Eetion to yicld boap.loside B P€da..lde (10- 

A., 9l n8), a a @lorl.s stite pow&r, 

St .: Colorls n..dle lik cryst b frm @lotrehci4 

M. p..251252'C 

Ialo t': +15.5r (c 0-024, MeoH) 

IR(KBr) r*m-r: l?53 (c{) 

w (MeoH) Lr, M (los e): 242 (2-E9) 

EnXI-MS ,,r/z 551.2715 (C,H{OD-H, €lcd 551.2735) 

El-Ms 110 eV tu/t (%): 752 (20), 415 (59), 331 (29). 169 (100), 109 (4t), 83 (4t. 

t22

'&Nre 

(cDclr, 300 MH2) ,, 2.21 (lH, orcilap, H-r a), L48 (l H. m, H- lb). 5.55 (lH, td 

Jr, F 82 Ha 43= a2 Ha llq,6.38 (lH, 4 .rt.,= 4.2 Ha H-l), 4.54 (1H, bt4 J6 - 4.t 

Hz, H6), 2.09 (l H, ovdlap, H-?., | .22 (t H, h, H-ft), 2.l9 (lE, ovdlap, H-8), 3.27 (l H, 

bd, JG,= 9.8 tlz H'10),2.01 (tH, E, H-l lr), 1.9 (lH, b, E-l lb), 5.16 OH, d4 ir4 

rf lo.8 H.,Jtaft= 6.2rVH-12),6.35 (lH, d,Ia. B= 1.0 Hz, H-14),7 34 0H, r,.,rr 

wr= 1.6Iq Hnt,7.40 0H, bli, H'16), 145 (3H,5, M.l9),0.90 (3H, s, Mc20),3.71 

(3H, s, oMe), | .29 (3H, s, ocOMcC-l), Glur 4.s7 ( I -H, .1, j! ,r= 8.0 H2, H-l'). 3.61 

(tH, oldLp. H"2'),5.ll (lrl ! Jt,,!ar= 9.5 H1H-l),4.96 (lH,l..l.:J!ar= 9.5 H?. H- 

4'), 5.04 (rH, ov€dap sisrar, H-5'),4.04 (2H, d, J6,!i 4.0 Ha H-6), 1.95 (lH, s, 

ocoi,le-c-2), 1.9 (3H, s, oCOM6c-l), 1.97 (3H, s, ocoM.{-4), 1.92 (3H, s, 

oCOMec{ ). 

'"c.Ni,a (cDcri, | 00 l{rz) ,r 25.9 (c-D, 66.6 (c-2), r i5.8 (c-3), 140.9 (c4), 4 r .0 (c- 

5), 80.1 (c6), 29.8 (C-7),499 (C-8), 37.r (C-9),4r.2 (C-r0),45.1 (C-lr), ?0.r (C-r2), 

124.3 (C-13), 108.5 (C-14), 143.5 (Cnt, 139.9 (C-16), 174.5 (C-17), 166.9 (C-18),28.7 

(c.19),23.? (c-20),52-0 (-cooMc), 169.6 (OCoMc{-l),20-5 (OCoM.-C-l) 102-l (C- 

l'), 72.0 (c-2), 72.5 (c-l), 68.5 (c4),71.5 (c-5), 62.0 (c-6), l6e-6 (oeoM.{-2), 

170-l (ogoM.{-3), 170-5 (ocOM.{4), 170.7 (oqOM.{{), 20, (OCOM€4,2), 

20.6 (OCOM.-C-I), 20.6 (OcoMcc4), 20.4 (OcOM+c-6). 

4,23,12 Bonp.to.i& C (1I) 

A n'&don non dhyl et.r., Fi-12 (3 d B $bjeld io sili6 gcl @lum 

chrcmtogmphy by Bing FhqN-cilyl .cdlte (7010) a lhe nobile phrs! lo obrain 

@nPourd (305 bd, vhic! w charrraird 6 boFFtosidc C (Sch.ft,3.?, PaSe 

r06). 

l2l

sub'izctiotu, F64 (1.4 d (Schcme3.8, P.gelo?) dd Bp-6 (l.l s) of th. bui.nolic 

cxdlcr (s.:hche3.9, P!selo8).1$ afrodcd bon!.t6id. C (6ll ms md 212 me, 

HFcriv.ly) by Nins @ycling HPLC (L-8q l:l HrO/MoOH,4 rnUnn! Ti= 72 mir). 

Th. cmbin d yield for borlDetolid. C OI) &om rhe th'* difr@nt iactiM m 71.? r 

ro{%0.t5s). 

Ph6t $/dd:71.7x lO' 

tht : Colorl.s 8ll@y solid fen heth@l 

ldln'. 

+2?.7 (c 0.022, M&rt 

lR ((lt rtu crr: 3406 (Gro; |TOE (C=o) 

UV (Meol0 Lq m 0og .): 213 p.a9) 

ERTA&MS Cv.) ,/z: 53521?9 (CrH'6ot rH, cdcd 535.2185) 

FAEMS Cvc) z/. 535 tM " Hf 

EI-MS (?0 cU r/z (%): 373 0 0),3s1 (12),341 Q\,325 l7),279 (2), 205 (34). l8J (lr, 

159 (46), l l9 (4 D, 105 (48), 94 (80), 8r (73), 73 000), 7 t (38), 69 (t0), 60 (95), 55 (70). 

'If-NMR (CD!OD, 300 MlIz) d: 1.82 (rH,44J|*A= 15.2 Ea Jt( != 8,2 Ha H-l a), 2. | 0 

(lH, n, d'lb),2.38 (2H, n, H-2),5.80 0H, !4.-3.6 Hz, H-3).4.54 (lH. bd, J6cF 4.5 

Hr, H{), 2.65 (f Il d4 J'! 1!- I 4.6 Hl J'.S- 32 rla H-1d), r.75 (l H, J,c7r= 13.9 tta 

.r4 !r= 6.5 Hz, H-%), 2.31 ( lil, ov.dap, H-8), 2.44 0 H, brd, joq ,0= 6.5 Hz, H- t 0), 2.25 

(fH,{l('l- 14.6 tia 4lq E= 1.4 H2, H-ttb), 1.62 0H..l,n,i- 14_6n1J$6- t2.1 

Hz, HrIa),5.79 (rE dd, JDq r tt r2.3 Hz Jt\nc= |.4 HzIj,-12), 6.s2 0H, bB, H-t4), 

7.46 0H, I 4J. w,6= 1.6 H4 H-I5), 7.59 On, brs, H-16), t.4t OrL s, Mdl9), l.t 2 (3I', s, 

Mo20), 3.7r (3H,s, OM€),4-41 (H, 4 j4,!= ?.6H2, H-l), 3.r7 (tH, \ J,h) o; 1.8 

ll2, H-2'), 3.40 ( l H, ! J4 r4t= 9,2 ltz. H4 ), t.?0 (l It, dd, J6tr ft= I | .9 ltz, J.r, tu= 4.0 

t24

sa Hib), 3.80 0 H, dd J6! trr= I l-9 Hz, J.c $= 2.4, H-6o'), 32c1j0 (211. ost P, H- 

3"H.5). 

'3c-Nr,R (cDroD, l0o MH') d: r?a (c-t), 24.8 (c-2), 1t2.8 (c-l), 137.2 (c4), 4r-2 

(c-5), ?8.8 (C-6), 29.5 (C-?), 47.0 (C-8), 36.4 (C-9), 37.8 (C-10), 43.4 (C'lr), ?1.4 (C. 

r2), 127.0 (c.13), 109.6 (c-l.t), 144.7 (c,lt, t41.2 (c-16), l7?.4 (Cnr, 169.0 (C-lE), 

27.1 (c-19),27.8 (c-2o), 52.0 l.cooM!), 105.8 (c-l), 75.4 (c-2'),11 .2 (c-3), 70.6 (c. 

4), ?8.0 (C-5),62.3 (c-6). 

313.13 E nD.rdi&G 02) 

Recycling HPLC (L-80, 1:l HiO,^'.OH,4 numin) *a ued for th€ plrif!.ation of 

FD3tsl (97 ns) fiotu FrL3 (5.7 & 25% M@H i! Hro), which 6rlt d in thc ielation of 

a kmM conpound boFperosid. G (12) (3.l E& I -9 x lo rTo yield, TR= 16 min) (schm.- 

l.l .0, Paeel09). 

P.r.. .g.yi.rd: 1.9 x 10' 

Si.L: \vLir. loqdcr fiom ftrl,ool 

ldlD': -12-40 (a 0.060, M€OH); {Lit 

-17.90 (d 0.058, MeOH)) 

IR (KBr) DIs cn_r: 3418 (GH), l?lq | 670 (C=O) 

Uv (MeoH) ld m oos €): 208 (3.62) 

IfifAeMs CE) ,t/z: 551.2129 (CrHqo,rH, c.lcd 551-2123) 

FAEMS Cv.)r/zr 551 tM 

- Hl- 

Er-Ms (70 evl,/z (vt: 388 (18r,37t (44),119 (t7),293 (9),265 A,24518),203 (28), 

r73 (31), 167 (39), 145 (50),ll3 (36),123 (32), I 19 (39), r05 (44),103 04),9? (48),95 

(81),9r (6r) 85 60),8r (9), ?3 (7r),69 (70),60 (67),5? (100). 

125

'H-NMR (CDOD, 500 Ml.rz) r: 2-92 (lE, dd,4q r0= 16.4 H2, iq 16= 6.6 Hz,lt-ta), 

2.63 (llt d, J,a n= 16.4 H4 H-lb), 6-42 OH, bB, E-3), 4.42 orl ov€d4, H{), 2.81 (lE 

4d hr1,. 14 4 Ha k,tu= 3 2, H_7a), l.E0 ( lE, d4 4q ta= 14 4 Ez, h4h= 6A rtz H' 

1b),2-39 (rH, dd, Jtc.a= 6.2, Jtc r.= L4 Ha H-8), 2.?8 (l H, n, H-i0), 2 21 0 H, dd, i,c 

fi- 14.7 E1 hLtu= | A Ez ll- l l!), l6? (l H, |H, J' lA n.= 14 7 tl1 hltu= 12 r [tz- 

H-l l b), 5.79 ( l H, dd, 4rc I0" l2.l Hz, JDq r h= 1.4 Hz, H- 12), 6.54 (l H, b'!, H- ! 4), ?.48 

(lH,trs,H-|5), ?.59(ln,q H-16),1.66(3H, r, M€-19), 0.98 (39, s, MF20),3.85 (3H, s, 

oMc), cru: 4.42 (r -tl 4 4q 2r= 12 rU H-t), J.r8 (rrt\ .t4 Jln.r'c 9-2 tE J2nb= t 2 

Hz, H-2), 3.39 O H, ! J.r, r!ft= 9.2 Hz, H4), 3.82 0 H, dd, J6,q 6 p= t L8 Hz' J6.q ,r= 2.3 

H2, H{'a), 3.71 (l tl d4 J6B 6!= I 1.8 tla J6r J!= 4.2 Ha H-6'b), 322-1,31 (2H, ovqr,9' 

H-l'&d H-5). 

"c-M'(cDoD, | o0 MHz) ,: i6.2 (c- l), 200.8 (c-2), 134 .2 lc-3), rss.1 (c4), 43.4 

(c,t, 7?.9 (c-6),29.0 (c-?),45.4 (C-8), 16.4 (C,9),40.7 (C-ro),45.5 (C.l l), 70_7 (C- 

l2), 126.8 (C-[), 109.5 (C-t4), t44.8 (C-lt, 141.3 (C-16), r76.4 (C-17), 168.r (C-18), 

27 -4 lc-tg),27 -9 (c-20), 53.2 (-COO!{e), 105.E (c-t'), ?5.4 (c-2), 77 A lc-1\, 1t.t (c- 

4 ), ?7.9 (c-5), 62.3 (C{). 

3.23.4.4 BonPero,ftl. D (15) 

Thc puidcltio. of $tsiacdon Bp4 (.100 Dd on dyclins HPLC (L80, 1: I H:O/}ieOH, 

5 nUnin) (schcne"3.9, Pas.-108) aforded conpoud 13. It wa also obliio.d Aon 

rtn tioB Buc2b.l6 to 20 (419 ns) by uins 6rrling ttrLC (OS-320, 100% McoE) 

(S.hm.-3.Lo, P.8.lO9). Thc @mhined l.ld of 13 Es 14.0 x 10{,6 (125 ng, Ta= ,14 

mi!). lt rd idoiified 6 a knoh conpound, bod!€loaile D 03). 

t26

P€rcenb8. yl.ld: l4,Ox l0' 

Strr.: ColorlN elid nln mlblml 

IalD'r -45./ (. 0.042, McOrDi {Lir -42.80 (. 0.(x2, M.OID) 

IR (KB') y- .n:': 3418 (O-H); | ?08, I ?67 (C-O) 

Uv (M.Oro L-. m (lo8 .): 214 0.5a) 

HRFAB-MS Gve) ,/zr 697.2708 (CrlLOr -H, c.lcd 697.2713) 

FAB-MS Cve) z/z: 697 tM - Hl- 

Er-Ms (10 .v) ,t/z (vrtt 771 (t 00), 156 (E2l 142 (?0), 325 (26), 264 0 6), 231 0 8), 205 

(64), 185 (20), r 59 (43), 12l (54), 9l (67), 8l (,O). 

rH-NMR (CD3OD, 300 MHz) ,: 1.98 (lH, bd, .lr D= 12.4 Hz, Hna), I -94 ( lH, brd, ,I|r 

r- 12.4 Ha H-lb),2.€ (lH, d! H-2a) 2.33 (lH, D, H-2b), ?.01 0H, r,J3.-3.6 Hz, H- 

3), 5.40 Od, Jd,- 6.0 Ha H-6), 2rt (lH, n, tt-AI 1.96 (lH, ov6hp, H-7b), 1.5? 0H, 

M..4,'= 13.4 Hz, H-8), l.3E (lH, m, H-10),2.95 (lH, brd, rrr rb= 5.4 Hz, H-l la),2.22 

(lE, d, H.ll'b),5.12 (lH, bd,41I- 8.0 Ha Hl2),6.52 (lH, d, r.. tr= 1.2 Hz, H-14), 

7.4r 0H,!4r.'{l- r-7ttz,H-r5),?_590H,bF,H-lO, l.l0(3H,s,Mel9), t.lt (3lls. 

M€-20),3.71 (3H, s, OM.),4.19 (lE 4.4'qr!= 7.4 H4 H€lc l ),3.85 (1H, dd, Jd.q dp= 

12.3 Ha J6q fu= 1.6 Ha H{'a) ,3.70 0H, dq J6r,6,i= 12.3 H?, Jr! rb= 5.0 Ha H{'b), 

4.34 (lH, d, Jl-q f ?.7 Ha Glc l"), 4.I3 ( lHd4 J5.a c!- I 1.6 Hz, Jn4 jt= I.6 Hz, H- 

6 a) , l.7l ( I H, d4 J6-r..!- I 1.6 tlz Js! rd' 5.0 I{2, Hi"b), 3.14-3.39 (8H- o!dl.p. H- 

2!H-5' ed H-2'-H-5'). 

"C-NMR (cD3oD, loo Mrk) ,, lz4 (c-t), 25.1 (C,2), 143.7 (Gt), 135.5 (C-4), 10.6 

(c,5), 84.5 (C{), l0.l (C-7),47.9 (C-8), 40.4 

l2), 127.9 (C-13), 110.3 (C-14), 1.14.3 (c-t5), 

(c-9),4?.3 (C-10),48.r (C-ll), 59.6 (C- 

141.7 (c-r6), r80.0 (cnD, 168.4 (c-18), 

t27

21.6 (C-t9),2t.4 (C-20r,52.1 (CHTCOO-), 100.6 (C'l ), 75.2 (C'2)' 78.0 (C_3), 71.8 (C- 

4), ?6-9 (C-5), ?0.5 (C-6), lO5- l (C'l ), ?5.1 (C-2), 78- l (C']' ), 72.1 (C-4)' 78.0 (C_t)' 

62.9lC-6\. 

12J35 Bonp.tdid€ A (la) 

a ftaction Frl2 (3 d ton th. cthyl dlai. .xtr&t w subjeled lo silica 8el €olm! 

chremlogaphy by si.g ^hciedhyl eltL 00:30) a tt @bil. phe R.D.ritivc 

CC o. sub-to&lion Frl2-M Gilio 8et) wilh 5-15% &elon. in h€Me (Sch.n€J.?, Page 

I 06) aford.d s ktuM @nFund, boEp€losid. C O{) 

(71? md. 

Bonp.tosid. C (l{) @ al$ obtain€d fron lhe sub-ft&rioro; M-3 (170 ng) (s.hde_ 

3.l. t, Prsrl lo) &d Buc2a (55 md (Sch@'3.1.2, Pascl I I ) of th€ blt nolic €xlret bv 

Eing @ycliog HPLC (cs-320. | oov. M€oH. 5 DUnia Tr= 38 mir) (99 ng and 46 m& 

r€sp.crively). IF @mbined icld of b@pcrdidc A (la) M 53.8 x l0{% (862 mc). 

Percsrl.gc yi.ldr 53,E x l0l 

St l.! Colorls gdny did nom nEthml 

M.D.t l7l-112'C 

IdlD': +5.9P {c 0.086, M€orDi {ur. +2.f (. 0.084 M.oH)} 

rR G3, v* m r; 3420 (GHri \766, 1729 \C4) 

w (M.OH) 1"-. M (los €): 20E (1.16) 

ERrA&Ms Cv€) z'r: 517.2050 (Cr6Hao,, 'H,c.lcd 53?.2050) 

FA&MS Gve) ''lz: 537 0t - Bf 

EI-MS (70 €v),tr/z (c/o):405 (271,376 Q8),359 \14),247 (13),203 (10), l9l O2), 159 

00), t2t (2?),119 08), 105 (22),95 (91),9t (20,8l O00),73 

(41). 

(5D,69 (14),60 (45),5J 

128

'H-NMR (CDrOD, l0O MH') t: 1.73 (lH, n\ H.l.), t.6l (lH, n, E-lb)' 2.10 (lH, m' H' 

2a), r.?o (r H, n, H-2b), 4.01 (r H. bs, H-3), t.o2 ( I H, dd, J4, ? s= tt.a Hz J6il1i= 4 4 H2, 

H-6),2.3r (rH, ovdp, n-?a),2.22 (lH, d, H-7b),2.?4 (lH, dtl. hnr"= t2A trz' ./r..1r= 

5,6 Hz, H-8), 1.87 (lH, m, H-lO), 1.98 (lH. dd, J|rr, rr= 12.9 Hz JrrA E= t l 5 Ha H_ 

I lb),2-17 (tH, dd,J'lauF 12.9 Hz, ilq 6- 4-5 Hz rU lt),5.86 (1H, dd J|k,,t= I l 5 

Ha 4l4,h= 4.5 Ha Hl2),6.52 0H, d, ft,6' l.o Hz, tl-14),7 50 OrI, ! 4'. '{r= 1.6 

rb H-15), 7.52 0H, b6, Hlq, l lo (3H, q Mel9), l.2l (3l! s, Me20)' 430 (lH' d, 

ia,!= ?,7 Ha rl-mnqio).3,67 (1H, d4 Jdt5t= tl9 Ha "/6t,Jt= 5 l Hz g6u)' l3l 

( I H, dd, J6 a 6,ri= I I 9 Ha J6'q ,!= 2.0 H2, H'6a ) 

'rc-NMR 

(cDpD, l00 rdtz) r: 19.5 (c-l),2E.3 (c-2),80.0 (c-l).816 (c4),473 (c- 

5), ?6.6 (C-6), 26.3 (C-?).48.1 (C-8). 36.1 (C-9),48.1 (C'10),45.1 (c.ll), ?2 3 (c'12)' 

126.1 (c-13), 109.5 (c-r4), r45.1 (c-lt, t41.5 (c-16), 175-9 (C-14, 180.0 (C'18)' lE 2 

(c- | 9), rr.l (c-20), 105-0 (c'1), 15.r (c-2),77.1 (c-3 \? t.4 (C-4), 78.0 (C-5), 62.0 (C_ 

d). 

32,3.4,6 Bonpet'oride F (lt 

suFnetion Fs-l (500 ns) frotu sePhld.x LH-20 6lMn (1009'" mre4 ofthe butanolic 

exir6ct, sho subjected to dycline HPLC (L-80, lrl HrO/MeOH, 4 nunin), afiotded 

conpou

Uv (MeoH) ln- M (log €): 212 Q t4),2o2 Q 65J 

HRFA&MS tF) '/z: 533.2021 (C,ItsO'r- H, olcd 533 2023) 

FAEMS tv.) ,/t: 531 [tt ' H! 

Er-Ms (10.v),r'2 Cqt 3'r2 (12), 355 (ll), 321 (8)' 278 (44r' 26r Q8).246 

(52), 202 (46), r45 (24), r2r Q2), 94 O00), 8l (6s) 

(t6\' 220 

rH-NMR (cDroD, 500 l'elz) d: 1.79 (lH, n' H_la).2 09 (lH, n, Hnb).2 37 (lH, m' H_ 

2.),2.33 (tri, m, H'2b),6 65 (lH, ! J].1= 1.7 Hz n-3),4 81 (IH'btLJ6 i 31HaH4) 

6-so {lE,4 4.d= l ? Ha n'D,228 0r! 't H-lo),2-30 0H' d4il', Ih= |46 HaJ''0 

rr.= I1.6 rL, H-llb),2 ol 0H, ddilc tr0= 146 Ha "rrrq o.= 3 7 Hz' H-lla)' 5 22 (1H' 

atrord @mDoDd 16 (1.4 6& 2.1 x l0r% yi.l4 Tr= 42 bin) (schers l-l' Paeel l0) 

Compoud 16 s4 .n.elqized s rtuthoxv'2-{p_Dstwp}rdosvl{l-3)'p-D_ 

slwopymGyl)-6-fmylrDmporyhi!. (16). 

P...6t.i! yi.ld: 2.1 x l0 r 

st 16 wlile poqdcr etd nm ndhdl 

M. p.: l5t160t 

ldlD '' 

-98.ao (. 0.066, M.OH) 

IR (KB, 's m r:3426 (o'r0; 1660 (c=O) 

I'v (M.oH) L! m 0os €): 272 (3 69), 2l I (4 10); lhb m: 244, 193 

nRF.SI-MS (+v.) n/z: 620.23 51 (Cr0I!rNOu+H, .tlcd 6202343) 

FÊMS (-vc) r/z: 618 IM - Hf 

fAFMS (+rc) ,n4: 620 M 

+ 14' 

Er-Ms (70.\r, /, (o \.295ltyr,28t (r7r,250 (2r), 231 (37 ), 223 (41), 194 0l)' 165 

(14), t52 (20), 127 (6), 85 (29), ?r (54),69 (3E),60 (69), 58 (100),57 (66),55 (4t 51 

06). 

rlt- ..d !c-NM& sa Table3.1.0 (seton-3,1,2.1.l, P.gc-89) 

3lj.,L8 ./V-Fodyl[omi!.(rn 

our of fina nciios (FFl to Fr-15) toD rbc clhyl aer'r. o(llst bv CC 

chmn.to8raphy, fr@iiotr Fr'5 (7 s) wls srbj@td 10 EFaled @lum cbhmarogtPhv oD 

silic6 8cl (5-15% EloAc in c6ED (sch.m.-3.?, P!8c-106) Io oblain whjre squ@ shaFd 

crysrals of.ompoud l7 (97 ng,6.l x lO{% yicld). Cohpoud 17 M chsmtcri4d s 

|]l

P.*.nt g.yi€ld:6.I x loa 

St t : Trmpardt squft dEp€d .ryials, &cionc.hcxde 

Nl, p,t 244-245'c 

IclD': -335.3' (. l.o, CHCI3): {Ln. -3460 (d 1.0, CHcl,)} 

rR GBr) Dd m-r: 1655 (C{); 1565-1425 (Nmdc n4} 1075, | 040 (Co{) 

w (EtOD rn m 0og 6): 3 | I (3.@),274 14.22r,2J5 (4.15) 

HR'EI-MS ,r/t: 291.104? (coHsNor cdcd 293.1052) 

['I-MS \10 .v) n/z \%r. 291 114r, 248 ll2),235 (100),204 (9), l?8 0t, 

l r7(7), E3 (13), t7 (25). 

3r3.{.&l (E!v-romyl,rodb.(17-E) 

149 (21)' 

ra-NMR (cDclr, roo Ml&) a 6.59 (1l{, s, H'3),2.&2.?0 (14 n, E-4J,2.E-2.70 0H. 

ir H-4df, 3.07 (r tL dd4 4q Jq= 12.9 g^ J*.a- rl.l tU Jb\rn 3.6 rL, H'5.J, 4-55 

( lH. ddd, 4q. r-= 12.9 H2, 4q, e= 4.5 Ht 4q. &{= 1.3 Hz, n-54), 4-58 (tH, dd, J6q t-' 

14.5 Hz, J.*, a{= 4.2 Hz, H-6a"J, L l4 ( I H, dd, Jta, *q= 14.5 Hz, Jt* tu= 14 5 Ha H_?J' 

2.83 ( I H, .rd, ,q. ,-= r4.5 Hz, Jrq e= 4.2 Hz,H-?,1,1 3'7.2 (tH, n. H'8). ? ].7 2 ( I H, 

n, H.9), 7.3-7.2 (rtl b, H-lo),8.09 (lH, dd4 4r. != 7.8 Ha Jn.t= 09 tVh.f, 075 

nz, g- | l), 6,09 O tl d, JF= 0.5 Hz, l{Cg:-O), 5.96 OlI, 4 JF= 1.5 Ha 2OCHiO), 

8.37 ( | H, !, OC[IO)- 

"C-NMR (cDcl',loo l"flt ) 6: 142.9 (c-D, 117.5 (c-h), 124.7 (cnb), 147.1 (c-2), 

l0?.4 (CJ), l2?.4 (c-la), 31.0 (c4), 42.1 (C-5),49.4 (c.6a), 13.6 (C-7), 135.1 (C-?.), 

128.8 (C-8), l2?.9 (c-9), 127.1 (c-10), 127.1 (C-ll), 130.4 (c'lla), 162.1 (C-12), l0l 0 

({rr) 

t)2

323.4$.2 

(zlN-FomyL0on.b. (U-z) 

'H-NMR (CDCrr, IOO Mlz) ': 6.55 (l H, 4 *..= O 6 Hz' HJ)' 2.84 (lH. 'L H_4J' 2 69 

(lH. (l(td, Jr4&= 15.5 rL, Jaq b- 3 0 H2,./.4,q= 1.9 H2' H4q)' l 17 0H' 

ddd' Jtu. 

tq- 12-6 H1J^\e= 126 r*}Jia.a= 3,0 Ha H{J, l ?9 OII ddq 44tu= 12 6 }lz' 

Jsq. o= 4.5 lla .t:are= 1.9 Hz, H-5a), 5 02 (tH, d4 J6a ?'= | 4.0 rr'z. Je\14= 4 5 rj2" 

H-6€J,2.79 0E d4 4-. '*= t4o E1&e= 14 0 n\ H-7)' 3 21 0r! {l.l' 4q r-= 

t4.O n2, h4e= 4.s E2;n-7 A,7 25 (lH, d\ H_E), ?.20 (lH, tldd' "b f 1 5 Hz" Je ti= 6 9 

Hz, Jr. l= L2 Ha H-9), 7.30 (lH, m, H{O), 8.08 (lH, ddd, i, . n=7.8 rr1 h.i= 0 9 H'z. 

' 

Jrl,r= 0.7 rL H_l 1), 6:07 (lri, d, JF.= o 6 Ha l-OCHro)' 5 95 0H. d' Jr= 0 6 tlz' 2_ 

ocH,o), 8.24 (lt , s, OCHo). 

'rc-NMR (cDcL, 1oo rrlr) rr l4l.l (c-l), llr.0 (c-la), 1240 (c_lb), 1474 (c'2)' 

t01 .8 (C-3), t21.4 (c3^), 29, (C4), 17.? (C-5), 53 1 (C{a), 16.2 (C'7 )' t14 4 lc-1^)' 

12s.4 (C-E),128.0 (c-9),I2?.5 (C-10),127.3 (C-ll),110.6 (Gll!) 1620(C-12)' l0l l 

GcHr) 

3.2.3,4.9 N-roruyld.tyd@!o!.b.(lE) 

conpound 18 (1.9 nc; 1.2 x I0'9'. yi.ld) wB obta,ncd a i66p€sr squ@ slBp.d 

dyslals fron fr&tion FFs (7 g) by $liq 8cl cdl@ chronatoSmphy (5-l5olo EtOAc in 

C6HD) &d chd&lerired 6 lhc ltloM compoud. ,v_fomyl.lehv

E pqibtuol ftta|otd dsPa 

Uv (M€oq r- M Cog 6): 156 (3.36), 130 (3.10), 2E8 (3-79), 286 (4 2?) 

HRII-MS rre 291-089 (cdtDl.lo! elcd 291.0E95) 

Er-Ms Qo e\) "/. (v,\: 29r (loo), 276 (6), 252 (El), 24s O3r,zJs 

(25), | 5 r O D, 102 O 8), 88 0 2), 55 (4). 

'H-NMR 

(CDClr 300 IW'z) 

(23),2M (40), 116 

', 8.89 ( l H, s, .NCEO), 8.9 ( I H, n! H-l l), 7.54 (lH, m, H_ 

lo),7.57(lH. n, H-9), ?.77(lH,m, H-8),7.22 (tH, s,tl_7),70a(lH, s,H-3),625 (2H, 

s, OCE o), 4.12 (2H, ! JJ,4= 5.9 Hz, H.5). 3.19 (2H. i. J. r- 5 9 Hz It4)- 

'3C-NMR (cDcrr, roo MHz) r: 145.5 (c-l), 125.6 (c-ra), 121.2 (c-lb), 143.0 (c-2), 

lo9.o (C-3), l25i (c-3o),29.? (c4),38.7 (c.5), 126.6 (c-64). I ll 4 (C-?), ll2 6 (c-?a), 

r21 .r (c-8), r27.4 lC-9), r21-3 (C- l0), 125.9 (C-l I ), t33-4 (c- I I a), 160.7 (C_12), l0l 4 

{4Hr) 

!.2J50 iY-Fooylrone.itdi!.(rt) 

Ftudon Fr-7 (4 g) fon dE .thyl a..t t cxrrsr B subjeted to tulhq @ll@ 

chre@togEphy on sili€ gel (3-10e4 .etoe in C.tld to obldin co@oud r9 (904 me, 

56.5 x I0r./. yi€ld) 6 a w e posdd !ftd !@siv. dlum chrcmalosnlhy on siliq 

gel. Compould 19 M ch@t€riad s i!. knoM @Fpound, iv-fomylnomkifenne 

(scbcne3.7, Pagcro6). if-Fomybomwifairc (213 m& ll.3 x lO*/' yi.ld) ws also 

ohaioai from A-6 (a g) ofihe €ihyl ectat €xirdct (SchemF3.7, Pag€n06). 

P.rc.nr.!. yield: 69.8 x lol 

S.tt : Whir. povda Aom *roG 

lalD': 419.4'(. 1.0, ct{ctr); {Lit 4l3.f (. l.q CHCL, 

rR Grr) r^ m ': 1660 (c{); l59Gl4O0 (ebliic tug); l t l0, 1040 (c-Gc) 

l]4

Elryana 

W @eorD r-. m (log r): 310 0.m,212 (2.Er),222 (3 \6),2@ lJ tEl 

EREI-MS ,,/z: 309. | 361 (CDHDNOT, c€lcd 309,t165) 

EI-MS (?o ev) "/, (70: 309 (62), 276 (2r,25r O00), 271 (t 0). 20? (?), 178 0 0) 165 

(19),152(6),58 (7). 

3r35.0.r {tfN-Fonyhom&ia.rioc(t}r) 

'H-NMR (cDcr3,3oo MHz,) d: 6.66 (lH, r, H-3), 2.91-2.?5 (lH, m, H_4!,), 291'2 75 

( I H. m, Had, 3.l5 (l H, ddd * a e1- 12.4 Hl Jt-,.n= 10 4 H1 J5s.a1= 4.0 H1H's-), 

4.4r (rH, dd4 44 b= f 2.4 H2, J'.-k- 4.4 H\ Jsa]q= 3 6rU H'54),4-49 (lH. dd 

J6\tu= r4.o na J&.la= 4.0 tV H{d.,), 3. I I (l H, d4 4& rq- l4-0 Hz, Jt& 6= 

Hz, H-7J, 2.90 (1H, dd, ,It.q. 

'-= r4.0 Ha Ja,6-= 4.0 rtz H-1d.1 3Gi 23 (tH, n,H'8), 

7 .36-7 .23 (rH, m, H4r,7.36-7.23 (lE, b. H- l0), 8-42 (l H, d4 4,. ,o= 8 0 H4 L. e= 0.3 

H?- H'l l), 3-65 (lH, !, l4Mc), 3.88 (lH, s, 24Mc), 8.38 04 s, ocso) 

rrc-Nie (cDcrr. 100 Mltz) r: 145.8 (c-l), 127.4 (c-la), 129.5 (c-lb), 152.6 (c-2), 

lll.8 (C-3), 124.8 (cld),29.6 (c4),36.1 (C.5),53.5 (c{s),37.9 (C-7), l35 s (c_%), 

r28.a) (C-8). r21.9 (c-9J, t27-5 (c-10), 128.? (C-ll), 131.6 (c-lla), 161.9 (C-12), 60.0 

(l OM.), 56-0 (24M.). 

3.235.01 (zlN-Fomtlnommir..i!.(lra 

IH-NMR (cDcL,!00 MHz) r: 6.64 (lH, s, H-3),2.9r (lH. ddd, J$,hf r5.2 Hz, J.-. 

'"r r2.4 Ez Juo s= 4.4 H1 H4J, 2.?5 (l H. dd4 Jl4 k= 15.2 H1 J.4 ss= 2.8 H1 

"rr4 Jq= 1.6 Ha H-4d, l.ao (rH, ddd, J&ri= 12.4 llz, Laba 12,4 Hz Jtqbt= 2 3 

Hz, H-5,), 3.?9 (r H, ddd, 4q != 12.4 H1Jja].F 4A LU Jsa(a= 1.6 Hz, H{q), 4.92 

(rH, dd, Jtu. r-= rl.6 H2,.,f6. ?q= 4.2 Hz, H{a!), 2.78 (lH, dd, Jtu.tf t3.7 Hz, h-, 

6-= l]_6 rrz, H-7J, L l l 0 H, dd, hqu= t!.6 Hz hq a= 4.2 H1\ H-1d,7 _26 \tH, n. 

| 4 0 

135

Eaetidtl 

TinaPddubry 

H-E), ?.23 (rH, ddd,.te.s- 7.8 tL, Je.ti= 6-EH1Jt.n= r.2 HL'j-9). 7.30 (lH, m H'10). 

8-,lO (lH. d4 Jr', 8.0 Hz, rL- 1.2 H"- Hnl). 3.65 (3H, 3, rOMe), 1.88 GH, s, 2- 

'0= 

ocHt. 8.24 (ln, s, ocEo). 

"C-NMR (cDcl,. 100 MBz) d: 146.1 (c-l), 127.9 (c-ld), 128.6 (c-lb), 1524 (c_2), 

Ill.5 (C-3), 125.3 (C-la), 3l.o (c4), 42-o (C-5), 49.4 (c4a), 34 1 (c'n 136l (C_7a) 

128-6 (c-8), l2?.8 (c-9), 127.1 (c-lo), 12E4 (c-ll), l3l-5 (c'l1a), 162 l (c-12), 600 

ooMe), 

s6.0 (2-oM.)- 

3.2.3,5.1 N-D.ndnyll-aonytLbydMom!.lf.rine(20) 

conpoud 20 (4.3 o8, 2.6 x lo'Vo yi.ld) ws obi.in.d by fl8h cc of fEciion FF5 (7 g) 

eom the elllyl &€iar. ext*t by 6in8 Sllt &.lotu in here, ard chlE ldi2ed a fE 

€poncd @b!oud, rr'{e@lhyl-,v-fomyld.ltydbrch@ifqitu (20) (S.hm._3.?, P.8.' 

r06). 

P.rtdlrg. yicld: 2,6 x lo_5 

St t r whir. F*dd frod s.toE 

IR(KBr) v* cn r: 1680 (C=O) 

UV (MCOH) l$\ m: 367, 348, 3 r7, 252, 205 

IIREI-MS ,/r: 30?.1206 (ClrHrrNOr crlcd 307.1208) 

Er-Ms O0 cD,/r (%); 307 (100t 292 (34\264 (26),220 (49), l9l 09), 165 (4E), 105 

(22),71Q1),5r l1OJ. 

'I'-NMR (CDClr,300 lvorz,) d: 7.25 (lH. s, H,3), 3.23 (2H, i,./i. f 5.8llz, H4), 4.15 

(2H,4, JrF 5.8 tra H-5),7.r2 OH, q E r,7.78 0tI, ovshp, n-q, 7.58 {2H, h, H-9 

dd H-10), 9.59 ( lH, dd, 4 r. o= 8.9 tlz, JlL,= 3.3 s4 Hn l), 8.88 (l H, 5' H- r2), {.01 (lH, 

s, 24Me), 1.93 (3H, s, l -OM.). 

l.]6

Itc.Nlm (cDct3, l m mL,) d: t 46.0 (c-r ), l5l.E (G2), I 12.9 (cl), 128.2 (c-la), 30.5 

(C-a), 38.5 (C-5), 128.a (C-6s), rr2.r (C-']. rr2.4

].2J5J P.pdilc 02) 

F@tioD Fr-8 to Frll ion th. edyl @t!lc Gxlra4l wrc funno plnfi.d bv @lunn 

chrcmiocBpht on silica gcl (lGl5% Eolc i! Fc.Hl, to yi.rd .dpoud 13 (2.0 ng' 

1.2 x loi% yi.ld) 6 a wlit powdd $lid (ScheF3.7, Pag.l06) Compoud 23 s6 

chdcrriad d , rcpoded tymirc a[.loid, p6p@ift. 

f.rulhge yi.ld. 2.8 x l0'r 

SLt t Vhire povd.r $lid tm chlorefom 

IR (KB4 vn d-'r 3620 (o'rDi 1648 (c=o) 

rry (MGOH) lj M 0o3 r): 308 (4.11),792 (4.t2\225 (4.t21 

HRf,I-MS r/z: 2E3. | 205 (c trH, rNor, calci 283.I208) 

Er'MS Q0 ev) tu/. (%r:2a3 Qt, 16,r (70), la7 0 o0), 120 (54), 107 (2?), 9l (38), 65 (24). 

'H-NMR (cDcrr, 300 MH,) ,, 2.6s (2H, t, J1,,- 7 .o Hz, H-?r,3.45 l2H, 

r, Js.r 7 .0 Hz, 

H{), 6.r t (rH, d,,I7. - r55 Ha H-7r, 1.39 lr'I, 4 J.. r- 15.6 rta H-8), 6 67 (2H, 4 

J!6./s- 8-6 na H-3', s\,7.27 QH, 4 Jr'6.rf, 8.6 Hz H-2',6\, 6.96 (2H, 4 .,r*, s= 8.6 

HaH-2,6),6.67 (2U, d' h,r6= 8.6 rVH-3,5). 

"C-NMR (cDct' t00 MItz) dr l27J (c-l), I 16.2 (G2), 130.5 (c-3), | 55.9 (c4) , 130.s 

(c-5), 116.2 (c-6),35.8 (C-7),42.5 (C-8), 131.3 (C,l), 116.7 (C-2), 130.? (C-3), 156.92 

(c4') , l10.? (c-5), r 16.7 (c-6), r | 8.4 (c-7), 14 r.? (c-8), 169.2 (c{). 

3,1.!,5.,1 N-tEFlcruloylttnbbp(23) 

Fn rioB F.-8 to Fr-ll fiu tlE.rtyl actr. dttut g@ @mbined srd sbjcd.d to 

FF*.n @lle chmnalogrlphy o! silio g.l (lGlsyo EtoAC in ,-C6HD) io oblain 

@mpoud 23 (401 os, 25.1 x 10{,6 yield) s ! colorlN 8llmy solid (Sch.m.-1.?, PasF 

ll8

106). InErpidation of spetd .rd physiol d.r! epporr.d @npound 23 a,V-td_ 

fcroloyf grrnid slrich B Prcriovly Eponrd frcn Ti@Por4 @ldilolia 

P.rc.nr.ge ti.ldr 25.1x lor 

strt : Colo.ld Srhny slid ion clrltufod 

rR (KBr) v^ ci-r: 32oo (GH); 1655 (c=O) 

Uv (MeoF) 

^.- 

M: 3l?,293,285 

IIREI-MS n/r: 313.1309 (Cr*lDNO. calcd 3 | 3. | 314) 

EI-MS (?0.V),/z (%)r3rl (13),248 (2), r92 63),177 000),145 

(30). 120(43), s5 (8). 

f 

rf-Ni,lR (cDctti€DoD, 400 !ôlz) 6.2.62 QH, \ h.- 6.8 tI\ H-7), l-5E (2H, t, ./r t= 

6.8 Ha H-8),5.5 (!hdotcoH),3.89 (31i, s, OM€),6.14 (lH, d,4 s- 156 Ha H'7'), 

1.06 (xr,d-Jz\s= 8-3 EzH-2,6),6.77 (2P,,d,J*.2 =E.3tt H'3,5),7 02 (4H, d4J6. 

3- E.2H2" J6.,- r.5 H1H4), 6.95 (1H,d.J/.6= l.5 rb H_2), 6 87 (1H, d,./t,i- 8.2 tL. 

H-5'), ?.50 (lH, d, Jr, r- 15.6 H?. H-8'). 

''C-NMR (DMso, r25 r'4rz) ,: 128.3 (c- | ), r l J.l (c-3, c-5), 129.5 (c-2, c-6),34.4 (c. 

7), 40.7 (C-8), 119.0 (C-2), 147.8 (C- 3'), 148.3 (C4), 115.7 (C-5). 121.6 (C-6), I10.8 

(c-7), 139.0 (c-8), | 65.a (c=O), 55.6 (oMe). 

!.2J.5.5 M.thyl-3,4-dibydrc!ybdod.(24) 

Fr&rioN Fr-8 ro Fr-l I 8on $. .$yl etst GXln t 94 losd.d d a siliq g.l @lNl 

md .luted wilh l0n5% e$yl er.r€ in ,-h.xee to alford fre y€llowish cryslals ot 

conpoud 2a (?,2 6e, 4.5 x loivo yietd) (Sch@.-3.?, P.gen06), Conpoud 2,r B 

ErystdliEd h chlorefom dd ch.nderiz.d a mcthyl-3,,|-dihydbrybc@aic. 

l.]9

P.|ga.g. tLld: 4.5 x IOr 

St.a.r tirc tdlowish 

crystals ffob chlNfod 

rlRf,LMS r/,: 158.0417 (CsHrO., c.lcd 168.0423) 

rAEMs (.v.) ,4: 16? tM'll 

Er-Ms O0 .\4 n/z (%): l$ tMl'(2.04). 

'E-NttR (cDclr. 300 rvlllz) ,: ?.63 (llt, d4 4 - &3 tlz. J6,= 1.9 Hz, H{), 6.90 0E 4 

J5.F 8.1rL, lt-5),7.53 ([r,44F 1.9 Ht, H-2),3.91 €H, s,4otttc),5.20 (lE t,3' 

or0, !.5 (l H, s, 4-OH). 

''C-NMR (cDcL, 100 lvflld ,r l2l.l (c-t ), I 12.4 (c-2), 1,16.4 (c3), 149.2 (c-4), I 14.0 

(c-5), l2a.I (c{), 1682 (H), 55.6 (oM.). 

3JJ!.6 cyfri!.&t 

re.tion Ft'.l (?00 og) tDh Scphldcx LH-20 collm (q!ld{.lbrnot, 2:l) of lhc 

burrnolic dir.cl M ponncd !y Bing Ecrling HPLC (GS-320, 100,6 MCOH,5 

nlJnin) to oblai! @mpoDnd 25 (5.3 dg 3.3 x loi% yi.ld, TR- 4l nin) (Sdmc3 E, 

Paclo7). Physi.d a.d s!.ctd ddr ill.I(dliott i€d r. ilE cndd.rizrlid of 

@Dpoqd a &. boM Elaid., crddi* (rt. 

P.ru!r.t!yt ld: 3.3 x l0_J 

Strlcr Colodcar 8umy $lid tom Eethalol 

lalDn. {29.t'(. | 2,Hro)i \rit- +26.f (. 12, It1o)} 

IInr EMS Grc) ,,r4: CeHNtOr-E Z2.0t5E (crlcd 242.0855) 

Ir{)

AIMS Cvc) a'zi 242 tM- Hl 

EI-MS r'l, (%): lal (4). l3l (l4), I 13 (52), % (9), ?3 (100). 

trl+'r,tr. (cD,oD,100 MHz) rr t8l (lH, d4 4q r!= 12.2 Ha 4,".= 2.65 Ha H-5'a) 

X.1t (lH, dd, Jtn!;= 12.2 H1 Jtr a- 3.0 Hz, H-5'b), 4 00 Ofl, 

dd4 Jajf 3.0 Hz Ja,],i- 

2.6rlz. J1.t= 3.O H1H4').4.r4 (ltL d4 Jl11- 1.0 Hz Il f 3.0, H'31, 4 17 0 H, d4 r,. 

3- 1.0 Ha Jt, F 3,O \ta H'2), 5 88 (l H, d, J|1 ,- l-0 Ea H-l ), 5 68 (1H' d' Jj,6= 6.0 H4 

H,t, 7.98 OH, d, J6 r= 6-0 H2. H.6)- 

!c-Ni'lR(cDoD, r00Mrfz)r:62.7 (c-sJ, .3 (c4),1t.3 (c-3),1s.1 \c-2),90.1 

(c,l ), 142.7 (c-6), 102.6 (C-5), r 66.r (C4), 152.4 (C-2). 

!.231.7 Syti!8ir (26) 

Tle puificsion of ft&ti@ Bur5 (300 ms) on ODS colum (RP.l8, sttlFmdhanol, 3:1) 

by sing @yding HPLC (L-80, l:l H,oM.OH, 3.5 nUni!) (schc3 9, PagcroE) 

allorde

ov.rlappins signal, hydrcxyh), 6.10 (lrl d! Jr. r= 15 9 tla Jr, r= 5 5 Hz, H-2)' 6 50 0Il' d' 

4. r= 15.9 Hz, H-3) &d 6.74 (2t1, bB, H-2', H.o) 

$C-NMR (cDroD, loo Norz) ,r 5?.0a (2 x oMc), 62.6 (c{"), 63 5 (c'l), ? I 3 (c-4)' 

15.7 (C-1"),77.8 (C-2"),78.1 (C.5), lo5.l (Cl ), 105.5 {C-2 , G6')' 131.2 (CJ), 135 2 

(C-l', c4), 130.0 (c'2) and 154.0 (C-3, c-5). 

3.23.5.8 5,7-Dlhydrcry-2"(+[tdmryPboyttsL_r_b.Mp.no_4{.c(2?) 

FEdon 16 (4 s) fron ta .lbyl @a1. ctt!&r wd $bj@t d to FPclt€d 6lUM 

chrcolloslnphy on silie 8.1 

(l-lo% @ioe h CdID. conpound 27 (8.3 n8' 5-2 x l0 

r% yi€ld) ws thus oblaircd s y€llow necdl. lilc fystils (scheme_3 ?, Paeel06) 

conpould 27 {s ch,ruicizd 6 a lmM @mFud, 5'Tiihvdmxv_2-(+ 

hy.lroxrlhayl)F4l'n-b.@parrn4{8. 

P.M!t g. yi.ld: 5.2 x l0_r 

srrt.: Yelloe nedl. lite cryslak fton &etoF 

HREI-MS n/z: 270.0522 (Cstlror, calcd 2?0.0528) 

Er-MS (?O .v) ,'/z (%): 2?O ( l0O),742 lt6), 152lJo), r2r (23r,91 0 5), 69 (28)' 55 (2?) 

rH-NMR (CDClr,100 MHz,) d: 6.58 0H, s, H"2),6.'!4 (lH, d,./6- 2.0 tl2' H{),6.1 

(l H, d, 4.6= 2.0 Hz, H-8), 7 Er (2H, d, h6.!B= E 1 n2,8 2',H4'),6.9t l2H' d' J!6 *' 

8,7 H2, H-3 , H-5)- 

3.23.5.9 Cy.lodeLnol(2E) 

fte heMe .xlt&t (60.31 s) M fi".tioEt d inb fint n&tioN (H'l to rl 50) bv €lllm 

chrcmarogEpht on norn l phs sili@ g.l, €lutid witn FIEMe along with thc gradidt 

of chlorcfom (t-loe/"). Repelitiv€ CC of fr4tions H-33 to H-37 (6% CHCIr in,-C6Hi, 

142

prcduced conpobd 2E (13.6 h8,8.5 

cnd.t.dad s crcl@c{rcnot. 

Pcr.mt g€ ylcldr 8.5 x lO r 

Sr!r.: Y.lloq o..dlc lik 

HREI-MS n/z CroH$O, 

426.3863 lcat 4 a263862). 

(Schcnc3.1-1, Page-lll), 

EI-MS (?0 .v) ,/z (%): 426 [Mf e2), 408 (4), ]93 (60), 381 (9), 124 0 0), 309 ( l5), 300 

(21),285 \14r,213 (9\,256

Ea'hdd 

T'BPq'ottPt 

6,4 yi€ld) s a etit€ pordd (s.h.F3.?, Prscl06) co6pdis ofsleual and prvsi'al 

dlb irdic!&d the conpou'd ro b€ l-@r-Dsl@ptrtusvlr{ilo€tcrcl (29)

CFIAPTER. 4 

BIOLOGICAI ASSAYS

4.0 

4.1 

Biologt.cl Alsay! 

lmmrDoDodol.aorf &3.y 

4.1.1 Inaroduction 

Chrpt€r4 

IM@ is drc body's defd. sysrd .gliost th€ tuf-tios or8ntris li Pmte.ts lh. 

orgdis fiom diFs6 by killing pathosd6 dd tmou cclh Now $e nodulaion of 

imw fDmrio6 dd rh€ tE6.!t of rh. di!.4 Elrlat io tmw sysrd @ rcry 

@mon by uine lh. n dicilrl ptots. t ha bc@ E68!l2.d that imwhoduLation is 

d.lt mtiE ro @nvdti@d ch.mihenly for a vdiety of dise3s For €xmpL djw, 

srch 6 phag@yrosis, Espirilory to6r ad orge uasplmLlrion 6 lBt *ith thc help of 

inmunotuodulatoioo. In c& of iFpd&d iMue sysen, th. @tiv€ oxygd sFci€s e 

scMtal, Btich l.ad kr FDnddve du"ge to olha tiss6. 

h h well uddtood rhat rhe mNt oI nodf, drug th@py mby l€ad to a nub{ of sid. 

cffeli iD Fniclj.r im@sopcsion lDd c'loldicity. Th.G @ etuin dngs qhjch 

c.e we*rry eti€iion of i@ue syslen &d tlui @y 6ue hyp€li4iti!. 

Bpo& or ltr. im@ syst m tfttli.b, A. A., .r al, 19871. TlFt fore, 

inDuonodDlsling lgdts @ 8i6 

sysr.D in baldce [Stiles D. ?., ,r ar, 1982]. 

to prd.nts witb siiiv. imuc s'scn ro kep llF 

U,mpora plan|s e mong lh. nosr r€lubl. hdbs in ryd.da 

ne

2002; Yotodq 'r., .t al, 2OOlt Csvin, A" .r al, 19981 dd imuohodulalo'v 

lMdjcke, P. N,. , ar, 2OO0; Malhd, S. and G. Kuttat, G, I99i Chinlal*&' O '.' ar' 

199; N.ia P. K. P., .t al, 20O4l &tivitict w. lh@roF d.cid.d ro *tlud' 

imuonodutlbry &tjvrty on djor @nstinmts ilolatqd fbn litotP,ta c.it d 

Thjr dgy w 6i.d oot by D.. M, Anncd Mdit .1 th. It Pejsru cdtd for 

Mot6dr Mcdicirc ad DNg R.grch (PCMD), Intc@tiodl cdt . for ch.mi..l .td 

Biolosrcd Sci@ 0qcBS), Univdity of K|dhi 

4.1: R.'ult! .nd Di!.u!.ior 

Cohpo@d! lcll, 13-1,1, l7 ad 19, i$Lr.d frc6 ltt$pota./6Pu, \@ l6tcd for 

iml|lModuhtory.ctivity by Nirs lmi!d-b6!.d chdiluiDAd@ 'sv [H.lfd4 s 

L., ., dl,, l9E2l. Hoqlg lh. !sl!t slow s lo* d iNi8Difi..tl ..tivitv ow a widc rgc 

or @n6nitio6 ( l-l oo F8/nL) in th. {nob blood (f.blc4 l, Fi8. 4 l .d 42) 

4.r3 Methodologt 

Th. im@nodultiory !.livity of dE cohpouds *$ 4dut d in 96wll flll_bottoDcd 

ni@pfar6 by si4 tbc st n&rd c.lEhiluiBs..@ !$y [H.lfdd, S L , 4 at-, t9a2) 

To r€sl th. cft.l of lh. cmpoud o! tlE phlg@trsis (O,{daliv. t{tn), lhe lmiml 

deFnd&tddilmnle$a. s$say B dplot!4 s deribcd by H.rud et al.6' 

Bdclty, rcutophil! (l x 107), spad.d in HlDlt bld@ !.ll elution eit! cdciu.nd 

hasEsim (tlBss*), wE iMblr.d wilh 50 tL of @hpounds @ngt.lioa (l l0O 

!s/DL) for l0 nimt6. To.!.h wll,50 ltl (20 nSrrl) 4mos 

(Sigtu chdical Co 

UsA), folloqld by 50 pL (7 x lO5 M) luinol (G-93E2 sigtu Chcnictl Co.) wo.dd.d, 

ed nFn HBss* @ a

T.blc:Ll: IrMulonodulatory ativiti4 of@mPounds l0'U' l3-la, lE dd 20- 

tce si.h vhol. bl6d $8/mL) 

lEDuoroddltort ..dvity thn thol. bkDd {Co!c P8/dL) 

E0 

P6 

iE . 

: 

E 

!o 

atoo ato 0'l 

Fi& 4.1: Efl€ct of@mpounds l0-l l6d l3l.l on oid.tiv. b6t im $tDle blood

I oourobodubrorr rctivir' dilb rhol. blood (Cooc. re/DL) 

fig. 42: Eff€ct of conpounds I ? dd 19 on oxidalive bs1 fbm whole blood 

4.2 Cytoto{c Asssy 

4.2.1 hlroducfor 

Cybroxicity is lh. a! ny of . suh6lde agaidr difi@l t}?€s oi ell hu!ftI !o living 

organjsm. The drue dev€lopn nl is verv €xp€dive &d im€ consMi'g p@ess ll is 

idponmt lo lesl dy suple fot its cvlotoxicig befot€ flv ifihcr screengs R€s.Nhes 

l@k lor ctloloxic @mpou& .ither lo ldll u@r.d dca *lls or to know unwled 

crrobxic etlel b.foF furrha ntdi6 in dsg dierdv ed this hclp to cho@ lhc optmal 

L nodem malicine" @q is curd by Eilg clloroic dtues A nmba of clctod'ne 

tlp€ fu4oditeqcnoids blre ben eporlld to Fss.s 

pol.nt etivirv agaiNl hut@ oBl 

epideftoid, medulla od @lon @et cell li.6 lst€visrv, C. €t a/ ' 2005i Shen, Y C tl 

ol.,2OO4i Shen, Y. C..,r 41,2OO5l A nwber of eGcscer aporphihe fld ivrmine lvt's

of oryourde nd wioE nw?o.a sPcics hd. .ltldv ben Eloned h fte lnolft 

tMiI, Y. D., .r al., 2006l. Ihlnjg thc pl!91sn|dv Dljor @pounds w rd'd as'inst 

borh rhe mml anrl ca|g @[ lis. TItu ssy m Frfomed 

san r a1 rhe PCMD, ICCBS, Uni@ity of K'fuhi 

4.1.2 Re€ulb ad Disculsior 

t'v M3 Smim AMul 

Conpomds 10-11, 13-14, l?, 19 &d 23 werc tescd fot cttotoxic aclilitv Gable4 2) Tn€ 

IC$aeainilthc nomal now cmbryo c fiboblst (3T3) @ll lin€ rc>100 F8/mL' shile 

lhe ICs against caMr @ll lie3 (Pc']) ws >85 * 0.20, >72 23 + l '10, >95 14 + 010 

pe/nl- for @Fpod.b 10, 6d l3, Esperivclv lac ICt vdu6 'g!i'sl hu@ prest'te 

callq (Pc-3) e[ lind fd odPounds ra, 17, l9 $d 23 B@ t00 !r/bl, Oable-4 2)' 

Tlw 6rnts & in !Md@ ro lh. EpdLd clrotoxic *tivilv of ctud' dichlooE rhoe 

e\ttt of Ttaospo.a tpeies, shcE . ninimd cfr6t @ ob$dEd '!rr'tno lbe 

ompound! *w fou/ lo bc tun-lonc b b.lh mtml oT3) a wu a pres[are @@r 

(Pc'3) @U lir*. 

4.23 Methodolog/ 

Cytoloxicig or 6mpou& m cv.lulcd in %-*ll flat-bononed micb'Plat6 bv Ning 

1he srald.rd MTT (3.14j{inclhylthi.bt62_vll-2,5'diph€nvl_reu@lim brnide) 

cotoineb,c a*y [MosM, T., l9E3]. ro. this purpos., 3T3 @lls (Mo@ FibrebldB) 

d wcll s Pc-3 clls (Ptusrate C.Mr) qqc cultured in Ddbe@\ Modifi.d Easlet 

Mediu, supplm€ edwiih5%of f@t l bovin erM (FBS), 100 ru/ml of Frcilin ed 

loo pslnr of slreplonycin in 25 .d flst, atd k pl in 57o Co? imbdlor ar 3?'c 

Expo@rialy grcwjng elts \|ft h.fun d, coutcd wilh hM@,loDerer ed diluled 

wi6 a parliculu medim. CcU .ultuF *nh ihc @Mrntion of 3 x lO' etlJnl- ws 

pEpar.d o

q@ us€d s d.ndards for II3 rd !C'l @ll lir*s' Epelivdv Aid ovmight 

incubqlron, ft. mediM w4 Movcd ed 200 pL of ftesn n'diu wiih difid'nl 

d6tdi@ of c@pou& (l-100 P$ And 72 h 50 PL MTT (2 Dg/nL) E add€d 

10 @h wU dd incubaled flnhd for 4 bs subseqMdv' 100 |l! ofDMSO w6 addcrt lo 

@h udl. Th. qt of MTT Ed@lid to f@'a tibjn c'U! ws cdcutat'd bv 

lll€€silg th. ah6ornanc..r t4O n4 bv uing I BicrepL e ELISA rcadq (Speln Md 

olus. Moldld Ddi@s, CA, USA). TlE claotoxicrty w E@lded 6 @ncs ration 

csins 5094 sto*'lh inhibilim 0c!) for bot[ 3T3 and rc-3 @[s (T$lc-4 2)' 

T.bldl: Ctloloxi.ily ofomPoods 1G11, lll4 l?' 19 6nd 23- 

ll 

ll 

T-- l l' 

l---l 

'st dnd ddi.rioo* !Sr.!&td dtur' 

rcs(|M)+(s.o.)' ] 

12.2t 1t.40 

lfi) 

i 't i I roo 

f =- 1 'roo 

re i >roo llSq 

-f 

0J1210.t2

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M. SchvE a M.; Arigori I. D, ConpdLB,w Ndval Pn lrcts Chedtttdce, 

D. E. Ed; Elscria: Na Yo.lq 199,2,7674{0. 

Mrhidol, C.; RwhiEwq S,; P6wl, H.; Pistnj.cDpotr& S.; Fng)|'gl S-: 

Chljffii, P.: Tergcbii$i, T.; Sirbid4 S.; Piclt4 P. P@ & ,{pr't ClEn., 19 ,70, 

2065-2012. 

. Meab

. M4.iakd, P. N; Joly, C I iN@!@4s Flbt npia,tuu'11'25+257. 

. M{ria T. S; Obt ri, K.; KrsAi,B-i''(tffi,K Pht@h.mitt t,195, &,l72v 

1136. 

. Marli4 T. s.: ohIdi, K.i K4i, R'Ys&!sti, K. PJtt@henct t,1996,42,l5t' 

158. 

. Matew, S.; C, Kutlr!, G, ,,ror.rdp ia,1194,70.354). 

. Maurya R; Mad6, L. R; cupt!, P.; Mist&, P, K.i sinan, c.: Yad.v, P. P 

Plltto.hnistrr, 2004, 65, 205 t2055. 

. MaurrE, R: w@n v.; K.pil,R S. r. lidian Ch.n. 5o.., 1991,7\,36r'364. 

. M@cn ry, 

41,1425-1430. 

M. D.; Blske, G. w.; B.i.w.tgcr, C.; FEycr, A. Heteroclcles,lg's, 

. M6t dd, s. R., Jouel o/ iE S.id. o! Food ad .t8ticdtttu,20t1,87,141' 

750. 

. Mdir, A. T.: t4y, S. V.l\'4nlal Prcdt tt R.poft,|t 2,9,243-285. 

. Mi4Y.D,;Cioi,S.U,;t .,K.R. Arch Plw^ Res.,2llo5,29,6274J1. 

. MotuN.T. J. Idnual. Meth.rb,l9€3,65, 55-63. 

. Nadkami, K M.; N.dhoi, A.K. Ldio Mat tia Medica- Nartopathic ard Eone 

. Nair, P. K. R.; Rodng@?. S,; R.tru4hddra, Rt Almo, A; M.lnicL S. J.j 

Escalon, E-; Gdia, P. l.; Wnuk, S. F,i R,ruhedre, C..ti( lrmunoph@nrco|, 

20M, 4, t645-t659, 

. N@.H.i Astgtun"s. t. J Bhbplw@o|,1998,62,7-t3- 

. N@& t; Mdimtq I.: ls[i!o, M.; Okitsu, T,; KondoL H.; Kyogotu K.: 

susavara, Y.Iws6li, H. Cr.a Ph@m Bt!l.,DA\$,2U42V4. 

. P-hal, P.; AdnrqA, z,; w A. H.tta M.tli@,19t2,58,l8a-187. 

r54

. ?aih.lq Ashish K,; Jain, D, C.; Shdl'' R. P, P/@@cdl( Biol , l9,S' 3l' n7' 

287_ 

. Patrddhao. B.; Vaidya, A, D. B. i Chorghade, M Cur Sctl, 2m4. 86, 789-799 

. Pavia, D, L.j Ldpd, C, M .i k)1 G. S. Ittodwtton b Spe.tor.ort; SaudeB 

cou€ge, w. B. co., Philad.lphia, l9?9,67.68. 

. Pqry. L. U. Medi.ltul Pla,nt ol Ean atul Soah E6t Ati.iMlT PBs: Cebridge, 

Massh!*ti!, 1960; p 268. 

. Pbnnry, t. D. Plr'to.rEntttry,200L, 56,231-243 

. Rng.s4 C. Y,i C!uz, M. C.; Culr Ri Rid@ui, , A. I Xur' Prrr'., 20ltl' 61, 5009- 

5n. 

. Rdl@, N. N. N. A.; fmt4 T,i Kojin , S; T.rdE, K.; MLshfa, A M. I 

E t hnoptr t N @ 1., 1999, U, 241254. 

. R.ge, N. N-; Paeblbhti, T, S.; Kullni, U. P. Prlod.r X.s-,2008,22,425441. 

. RoMic\ L; Kis, K.; B&hd, Ai Ei*ntich. V. C@ @,4 Ct a ,a'r,2mr, 5 

515. 

. RotuE4M Nat. Prc.l R.p.,199,16565-574. 

. Rolna, M.i I

. Sk4 Y. C.; ChoS; Y. B.: Aln d, A F.; t c" C L.; cLen, S Y.; Chid, C. T.; 

Ks, Y. H,; T@g, G. L. J ,vat. P@d. 2005, 68, 1665-1668- 

. sh4 Y, c.; vaE, c. H.; CherE, Y, B i Veg, L T.: Gun, .t H; chi.n' C T; 

Khalil, A. T. J Nit P'od., 200{, 67, 316-12l 

. Siddiqi, M. A-; Nsn, E.; Al! S. L nqo of West Potdstni F@4$: I

SECTION B 

CHAPTER 5 

O-ia.*.t4.tt'-'. .tqDL 

= =---: i i= 

= = 

--Ei=

Chrpt r 5 

Applic.tion of NucLophilic clt lysl, to the Asymmetric Generltiotr oI 

Qusternary Ster€ogeric C€rt€ru: Towsr& th€ Form{l Tot l SvDthsis of 

C)-Physos.istniDe (9e). 

5.1 Cat lysis 

5.r.1 IrtroductioD 

IlE g*61i6 of dkarbon quaiffy sicr.ogcnic qi.ts prcets t chdlogp for 

srdnclic Edlb6is dE to slctic Epulsion bc$a th. c!6o. subdlrM|s Wl€n rb. 

fou sbslitEnts difer, lhc gd@tion of qud.Mry std@@G6 beolm a sincular 

chalLng. for asymclnc ayltlEg lctubloffd, ,. & Mlti|, A", 2001; CoEv, E J & 

G@m+@aA.,1981. 

'ItE derlopEd of dlb,llc n€:tltd! for 6ym.Eic sltth6b is oft or tbe fomsr 

activiti6 in org@talysi. Pio@i.g w* in Ub fi.ld sG Micd our b, K!owl6, 

Noyori dd Sba+t.s, .sFcially in rh. dcvclopD.nt of €ial)'tic dyormlric 

hyd&gdation &d on&dor Howv.r, @l.tylic 8'M.lric berhods for lhe gd€r.1ion of 

c4C bondr sttl rced 10 be lrudi.d atrd d€!.loFd .xh$v.ly to &hicve the etredive 

syntn€sis of biologically &dv. orlrnic conpoudr [.t&oben, 

E. N,. el a/., | 99]. 

Duing ll1e pEsd shdy, thc chinl cob.lt .a1.lFt wa 3ynihesizd d14 .pPlied in O/C@y 

Fddg.m€nl b genenle the rcquir€d .ll-cdbon qutem.ry sleHgenic etler. A key 

inlem.diat€ for the syndtesis of biologicrlly etiv. pyrcloi oline class of natural 

produc8 wa also synthai@d sladvcly in 99lo .e,

5-l.2 Nucl€ophilicCrtrlFi! 

Nu.lophilic €lallds fwiion by d@ling ,! cl@1rcn pair lo 

nEl6philic @rrlys$ tlo not .b.tt .t a potoa ilon 0F $bstat 

20061. 

'I!e n@l@phjlic mtlr€ of pttidiE in eddlitrg &yl.don @ijoN m dis@v€Fd in 

l8d cnruy lvdLy, A. ed Bnbing, F. l90l]. Gold &d @-worke6 in 1953 dis@ve€d 

that plridine cm cataly* $e hydslysb of a.eic lrly.ltidc 30,000 tin6 Iaslcr thd 

{€ta1e dion, .vd though tyiidirc and @r.l'' hivc aimilq pKd vdws [Bafn4 S L dd 

Gol( V. 19531. In .dditiotl il ws disrcdd thlt lh. hot bai. 2_pi6lire dd 2,G 

lutidi* e bolh cal,blietly id.dvc.'Irr* obw.lios Ld to lhc dcdldion of tb€ 

Nl@philic .at@ of ptridi!. b.scd crt ly{* I! llc *yl.tion r.slioD a nulophic 

carlbsi 6sr displG e @|rL elo {.tic .th}drid. io fom lh. e.tylp}ridini@ 

db& (92), folow€d by hydelrsis of Ob inadcdirr. !o fom edic &id and 

EsclMdon oflh! pFdir. 6r.ly3t (SchdF5. D. 

tl 

g 

l"?-""^- 

92 

sct.ne5.r: Msheis ofhydolrsi! ol@tic dhy&idc c.t lyad by pyridire. 

5 

t .5 equvi EtrN 

-\ 

Hro 

c dy.t pyridiF >5% 

DMAP(4EDI7' 86% 

O-

MuuSe in 2o0l md steSlich in 1969 Eponcd the ability of DMAP 10 cataltz difil.ult 

ryladoB IMmgBn, R., gl a/., 2003 and Scglich, w, et al, 1969l nildqEd t niarv 

al@hoh ruh 6 I'o.th/cyclohtul G mt acylared wilh @tic ohy&id. in th. 

p6cne of stoichion Eic pliidift. h @trst, iq[Iar of n thylcyclohml *ith jlst 

4 mol./o of DMAP dd I .quv.lol of bic0ryldie 6died in 86% acyation 6ia 16 h 

(.qudioa l). The dialkyl@irc greup of DMAP is thN EsFlsible for the cddcld 

drltric *livrty of DM-{P ovd pyndift [Ho0c, G., ., al., 1978], 'Itji m@ potdtial 

of DMAP ircr€66 tle nu.Lophilicity of the plridire nicogen ed lhe.efoE fi. mle of k, 

rd ddirioD th. lgll,e stalilia th. ilam.dia& ior p.n 93, Thc m@ siabl€ ion pan 

93 is 16r @dw thm intcmedia& 92, s lhc in.Ile in lhc aladve de of DMAP ovcr 

pyridin h dE to the inc|le in cotucntratiotr of the inicm€diate t3 (-5-10/.) d 

@bFr.d b the reelisiblc @!'@tBlio. of 

't 

in m'tdd elvdrs. Irie w[ for n@ 

@rirc pFdi6 ba dcded only a f.* $ructu6 *ith higlar cairltlic &tivily 'I'd 

DMAP. These pFidines contain 4dim substii@tr with idcl!*d cs@a@ donadon 

into d. plridiE dns (Schd.'5.2). It is kms tht @nfomariomlly rcsticted plridircs I 

dd ll (S.hd.'5.3) uc doE rdiv. rhe lhc DMAP, baae ila dino tubst rql 

holds $eh in a @nfomtion which is flvou.ble for EsMa sth the prridinc dng 

(TablF5.l, oEi€s 2 and 3) lHeidich, M. R., ,? al., 200]1. 

o--'"'"-*l*"f.."'. *f 

sct.b..s,2: Hydrelysis of e.llc dtldnd. crulyzed bJ dimehr luimDridine. 

,3 

159

0 

&rN 

ScD.DoSJr Acyl&otr @tion by dif.r.nt +djmpyridine cloltd dendives. 

Th. mrw of &rl donor aie afiers dF r!r. of DMA}{,lalfrrd &yLlion @doN 

[Hofle, C., €r aa, l9?8]. Acayl chloddc dd DMAP qMrirarivcly fom d ion paii, 

ealogos to 92 in nonpolq $lvab, wheM @tic ditydrid€ dd DMAP only rom 5- 

loelo of the ion pair 92, Ho\lffi, tbi5 ift'le i! odqrlation dcs ml l@d to a 

@nBponding ilrcl!4 i! t!. raL of !cyhri6, Depir. rn€ |dac dircH6 in thc 

colenrtnrior of th. Fn t, ihc DMAP oralyEd @yladon of cthynylcy.lolq@l 

'on 

wilh AcrO is th@-fold fslq tne with AcCl, ft. incrcNed Eactivily with Ac,o is due lo 

th. dion of lhe ion pd! duing the d.nd.mining &.omp$ition st€p lo fom lh. 

&ylarcd podet (Fie. 5.1). 

T.blcs.l: Rcladvc dles of@ylalion *iii +minoplddim dalysl ddivatiy6. 

DMAP I 

2 2 

l Il 

Fig. 5.1: An inEmai.re in DM^t{ulr&d eylarion tudoN. 

o)

5.13 Cbirrl Nucleophilic Acyl Trrfffcr Cat bs.! 

'nE hi8hly c@li@ldtive &yl E6fd @lios M initiallv studi.d bv Vcd.js ed 

chq wcd.js, E. ed Cne4 x., 19961- .4 nubd of chiml DMAP ddivtrivcs q@ 

synrhesi*d ud wd in the dtlm€hic &yladon dujng lare 1900's ln 1998 Fu ddcrib€d 

&e fi61 emtioelectile v&idt of fte O/C.csrboxyl G]lfugmenl *ilh @la.toncs bv 

EinS ple& chnal DMAP c{.lyst 96 lRubl., J. C. ald Fu, C- C , 19981 

Bwy| ml cutD!i16 9,1@a.lo C€boxyhr.d a?,ltcron 95 in high vicus ed 

good sl.cdvity fsl.gtich, v.; Hoae, G., 19691 (Sch.@5.4| 

I 

95 

93-95Vo 

EE-92Y.a 

scLbF5,4: Resndgemdt ofazl&tode.d.ivcd mlcdbomrA vifi chiral caLlvst % 

Reentt, Ri.h.ds goup [Nsuye4 H. V,, .r cl., 2006] also sodi.d O/C{dboxvl 

tlafug@nt with 6z.l&toB bt 6inB mFpl.M .liral DMAP stdyn 105 (Sch€b€- 

5.5). In l9E?, Bla.k €pon d dc crldEion of t}is lyF of O/C altoryoltotrvl 

@s.n nr '@tion !o b€@fumoft r,.cns [Blek, 

96 

T. H., er al., l9E7], sinild lo $e 

adteton€ scri.s. Ir w repoaed 1hat th€ ir&tndt of the o-€boxylai.d b4@fudone 

(97) with DMAP (-lo hol "/t caed a 'aPid @n6ion (2 min) 10 th. c{dboxvlaled 

b€mnmon 9E.t m6 rdFr.rw (S!h.m-5.6). 

DuiDs tbc pr*nl study, 3,,kj$bnn(.d chidl DMAP st lyst lO5 (Fig. 5.2) wG 

stntheeied cMtios.letiv.ly i! 4 st p3 &m h.x!e2,5d@e (106). rhc c6Llyn 105

B applied |o de gcrcrdrio. of dlqtd q@t tuty 

9{ 

107 

x=.'-€ 

*..P* 

l0s 

F+ sl: Chi6l DMAP c'r,lyd llxt. 

ai'-** 

F/-@ 

--p* 

/5rdtutic $4th.tit 

3r.6gdic ent r rr c-l of 

T-\ 

t0l ri1 

Sctd655: Sldich tamgc|qt of 4&yl.Ld @la.roB wilh clolyst r05- 

n 

R = Mc, Er, Bn, Ph 

DCM, I min 

8G% 

S.bd65.6: Nucl@phile cat lyzd O/C.&yt edmg€mdt wifi DMAP caratyst, 

162

'nr€ chihl vc$ion of DMAP catalysl, synlh.liz.d by Fuji &d cowo*fis [Fuji, K., sr 4l 

19971, wa modified by Spiv.y, wh.r. tughthyl Srup wa idrodu.d a..hiral 

auilis.y [Spi!c, A. C., d/ rt, 20001. fticlt 3Mi!d ,rv41p]tidinvl{_!t dtvl prolin. cl6s 

of chi6i.alary61! for srl|Ntric Orlc-eylrc{r48.66t [Prid! G.,.t at. 2I03l. 

'nErc @ sitr.l rcpotu dffiibns @C-i.yl tlirug.dt nt in ildoliHkeldon dd 

&alo8oN b.@flmonc d4v.rirc! 1o gcndt C-l t.gt'rmtric @nr!r [Hills, I D arld 

Fq C. C. 2O0l; Shlq S, A., .t .1,, 2003; SIue, S. A., .r 4I , 2006; As*.vi, K , €, 4/ 

2oo8; Aslinoi, A., €r zr., | 981. Duing 199&2007, moE thd t00 publi.atioc dd o@v 

ni€s in syt|Wtic &yt lrdsfd @tiod h.vc bei Publishcd lComon, 

wuraRPC.2004. 

S. J 2006; 

ln this onrcrr tt. ptlgt nudy B 6icd out io filxl DoE &livc ad hiCv eLcliv. 

@b.I et l'sB. OplitM @nditioc for good Bdls by wi3tio. i! !ub6:taL sEudrc, 

elEt &d anFihc re rle 3ndicd. 

5.1.4 Qurhrmry Stclrogcric C..ten iD Asymn€aric Sytrlhetk 

Moy .lt loidr @ sin r qurffiy C-3 in indolc or oxindol. skclcloq a c{@plilicd by 

(-IpeudophrrDdiml, (-! nuslrdie B, (-lphystistue (99), (-lphcMirc (100) 

tHMs, A., ., or., 20041, C!*@rhob (r0r), C)FhoBifilim (102) po3r&s, ,{., et ar' 

l99ll, m.l.srsheift (10!) tc!n4 M. R &d RMivo, P., l995l,.d di@ide a 

(r00 [Li, J., ., 41, 20011 (Fis. 5.3). Th. inLFsdng suuctunl mtifs ald psnhiry 

biologic.l &tiviti6 of th* .lt loi& b.v. motiv.r.d $iddn! to &v.loF syEnctic 

Dqt6 to such qlrtcmliyebon bo.ins oxir.lol* srd idol6. Only f.v neidqi'lys.d 

q{rh.es h.vc be.n Eponed for th. 3,3{bubstitutd oxin.lolca i! litcntuF [Pou!$4 r 

8., ,/ ,/., 2007; Ashino , A., ,r ,/., 1998; Do@y, A. 8,, .r al, 2003i Le, s. dd 

Hdwig, J. r., 2001; Trcsi, B. M. ed Fcddikso, M. U., 2005i Tbsl, B. M. &d Zhms, 

Y., 2006; TD6q B. M., ., al., 2007; TMt, B. M. dd zho8, Y.. 2007; Co*cy, B. K. od 

t6l

Tostc, F. D., 20071. ftc chi6l trwl@philc{a|.lyed ttllfugm.nis in O_eryl oxindolc- 

d.rived cnolales to C-@iyl oxindolca N odidcrd ro b. a Powitul rcule to thc 

sl@Flerivc syoihcais of (h* quL@!y c&hoo @loinins slkiloids (.qution 2). 

*ff,,1* 

R - CONHM., Clphy$dismir. {99) 

R = CONH?I C>ph.enn. (lq,) 

R - Mc, Clem.thol. (r0r) 

Fi& 5J: Nllud drdoids coni.iniDg e .llsbon qud.m.ry sl.@86'c 6t r. 

"4.4.-" 

Th. tl.rusd.nte ir oxitrdol.ndiEd @l {boE14 d. tuch slow a @npar.d to 

th. @Gpoodio! aal&ton.- dd bdafqtu*ndivcd.nol crboal6. ftb diff@n@ 

@ be expbiEd by th. difr@nc. h thc silbiliry of0E cortspondinS ion pai6 duins $. 

Ea@8.o.nl3 [BordB.U, 

F. G,; Fri.d, H. E,l99l!, 

:l 

a."#"** (2)

Tl@tuE, ii E NuD.d thal a gcrad 6Pid syntBis off* 3j{isubstituttd otjldold 

by Nins a redity av.ilau. chinl nuloPhilic drlyst rcmiD.d ! prcbld to b. elk4 

.rd e appopriarc $b6far., o&lysl !d @c1ion @ndiiod n €d to bc i

inknediatc 6on rl? ed b€izyl chtorefoml€, fte $bslitulcd ptoduct U8. vA 

p'ods€d by ihe €linietion ofCO, and HCI (cqution 3) 

@ 

aH 9lr. 

..--,,.< ". ,-,,-_< 

,0, 6" ro! o,t fr:i'- 

d 

I^ 

@'' 

m-Ea' 

".J- 

Ar". 

l" 

er'.-l-n 

Sc[.nc5.?: Sleps ir sy.ih6is of chiFl nElophilic etalysr 105. 

Raclior ondltion.: (a) Ba!.rt y.as! sG|@,Hro, rtj (b) E!N/DCM, Mscl, HCl, -20 

'c; (c) NBSMCCN, NaOH(q, G (d) DCM/EIOH, (M€CqrHg, LiCl. 4 (€) I"DCM, 

Nars?so.; (0 NaH/THF; (s) ,-BuLi/THF, znCL DIBAL. ?dch(PPlbr, -78'c. 

155

11! R- h.ix, (-R-qqjrcct$r 

!1&R'p qcrB.$x lirdRr3i3*. 

S.h.Des.E: coNdion oflv'nelijyl-4-hethoxyemliF (l ls) inro c-&ylated oxindols 

Addirion of5 Eol% ofcaralysr 105 to IlE in lolud.r'dichlosnerhaN (lh.l.tter slvot 

E r.qritld lo elub ize lhc sbs6.lc) 6dr.d itr a cld lt!fugetrmt io I19. in 4E% 

e (T!blc-5.2, mFy 1). R.pedtion of rt t*riotr .r 0 "C tieldcd no Fodel {dt , 2), 

whil. tlE e of diblmbetttu .loE Bultqd .n * of 48% (dtry l). 'nF c wa 

incr€ed to 57% in THF eirh s sigrif!.drly longd Eaction tine ed lo@ yield (enry 

4) nte rcpleed€ of rhe phoyl wboBl! ll& wirh dE Anilrophoyl Md benzyl 

@ng6ers, llSc and U8d, led to tu €@rioslectivity (€nties 9 ed l0), lo conirsl i1| 

lrichlob-rer/-butyl a&loe@ rrSb yicl&d ! 50% .c in blwre (wirh 10 molvo rftt, enlry 

t, hul nEh loM .@liosl@tivitis wE oh.incd il nqaDddichl@m€th4 or THF 

(cntriG 6 dd 8). fte polar $lv.d r-oyl al@hol I found to b. wilabb fo. th. 

@rion (.ntr 7). By ui's lilhjM hydend. bcdill.d l!/dmlFis of cMdlruicM 

.std 1l9r ed rt9b, dc csulring &ids 120 lNfr found to @trtain th. sfu mjor 

.natioDq by chirrl iIPLC tuElysis. Th. alsolute confisution 13 tenrariv€ly Ni8red 

lo b. S in compdrien to de mjor c@riom Gulting frcn tbe Eamg€mdt ol O- 

I 

{

!4yfat d ,zal&to6 Pith calalylt 105 lNsuyd, H. v , ., 41, J or8. L.tt 2@61. Otbd 

dab{rr $to u*

Recr)6t llialio! of r19. (4E% ec) non IFxedl'P'oH vicldcd eqnio 119. ed ! 

tulhcr liqsr @Eisring dmst crclBivcly of llF @jor cMtiohd (Sch.F5.l 0) 

The N of prcfcMtial crysLlistiod io sprr.t ilF .na iffi &ob ! @nic 

@dpourd (s @pos.d lo I @hi. hixr@ thrr fom. @n8lm.d.) ha ffidv b*n 

dcEosdal4 &d qui6 lh! w of & clrttiMich.d mixtur. of .Mlim.6 [LoEna 

H., ., al., 2006; Polastw. D. 20071. Alo$lgh th. ..ttriioeleiiviv of th. O/c_&vl 

tElfuga@r is EtaliEly ood.d, t!i! ctyn llislid P@.dut Prolid.s . higNv 

.@rio+rich.

53.1 

53.1.1 

Erpcrimerril 

Gcneral Erp.f ncn.rl Proc.durc 

Pnor ro dE N of orerdic slrcds lh.y 96 &icd bv drshl.tion i! lb. ptE*@ of 

vdiou dryinc asmts THF w dri.d oq sodiM wia in the p!!ge of b@4Ph€nonc 

CaHr 6 !s.d lo dry dict orem.thsc (DCM) aid DMF, while rolMe ed EtrN w.E 

disriU€d ov€r nolter sodid- All oitEi slv.n$ ed chmicals wre ued a @eived fbn 

rhe suppli€b (Si8!ia ALtrich) wi$out funlM puilicadon. The com@iallv available 

(sisno Aldrich) sllniotr ofbutyllilhih (2.5 M h h.Me) dd DIBAL (1.0 M in h€xme) 

*s !s€d. Analrtical Crad. elvdt! v@ u$d for th! puifietiotr of 0E ctrion nixtw 

by Bing sili@ gel @llm clmn.rognphy, HPLC grade $lvdts wE u..d for tlE 

aElysis ot @tiom.ric sc* by chiEl HPLC. All E!.tios wa Fdoncd uda 

arnosph@ of tri[rgs or agoo io ovd{rid gl8s9@. 

5J.1.11 Cbrun ognpny 

Thin hrq chrcmaloellphy (Ur) E c{i.d olt {ith Ki*lsd 60 F254 (Mcrct) 

alminiM shers and @ alElyztd und.r UV hnp 254465 m. A solution ofvuilli. (9 

g vdilli4 150 bL EtoH, 5 mL H,sOi ed 40 mL Hro) s us€d 10 stain TLC lal€s. 

collm ctuo@rosmphy w6 perfoB.d on silica 8el 60 (40-60 and 230400 Fn n4h 

AS IM) cbinl HPLC m Frfomcd on . ChiEl@l OD colum. 

5j.l.l3 SD..rMpi.Tabiiqu6 

lnfi&€d specba qeE @o.dcd on a Shin da F'[R-E300 intur€d sp€ctrophobneiet d a 

n t liqud on Nacl dis &d p@r.d i. cn_'. Alt NMR sF.lra wE mrd€d on 

vsie NMR (V@) sp@t Doad (loo for rH- ad 100 for rrc-NMR) a! dbidt 

khFBnrrc. The cl@i.al shins lalB @ gih in t (ppn), Efm.d with 6ret lo

|he cidut elvc sisral (CDCL), whil. @uPlin8 coN!.nrt (4 wcrc m€sur'd in Hz 

M6s s@ra !w reorded at EPSRC ns sp.cto6.ry sflie (svaN., UK) 

5.3,1.1.,1 Phy.i.rlcoltldtt 

Melling poinis wE d.tomincd on GaU€nlMP (El.ctronic) delling po'nt lppaatu 

Oprical tulliios w€E r@td.d by using a Opdcal Activrty AA-1000 poldim.&r i 

c omfommd @n@oirarion(c) wa$r€n in g/100 nL ( v) 

5.3.1.2 

5J,l2.l 

St Ds i! tneSy h.rb olchinl Nucl@philtc DMAP C.ltlvlt 

Sy l6bof 2s,5s-A.r!diol004 

A nixrw ofB'rcr's yeasr (60.01 d !d lsGa $lltioo (100-20 

s in 520 sL pard) 94 lakd in 2 L dicsl llak- Thc mixrw 

w sh,rd wU for on. hou fouosed by ih. addino! of hcr,F 

2jJim Go6) O.o hl. 25.57 !@l) ed snild for 24 tours' 

befoE th€ ldcilion of seoe slutio! (?5.6? g sos in 130 nL walq) Amlld Frriotr 

of hc@2,5-

53,t,22 

Slattdb of2SiS-H.n dlol dld.O.tr4lromt (108) 

A eludon of 2s,5.t'hextncdiol (roD (0.7 s, 5 93 mol) m 

F.p4.d in dichl@rh&c (10 nL), fotlov.d bv lddiion or 

EtlN (1,?E FI" 1.3 g). TL $ldion B 3ritld wll {d cel.d 10 

-20 eC b.forc rh. addiion of oct[ykulf@yl .Udid. (092 Dl- 

ll.8E t!ml) in drcpwi* f.shio. oE e hour with contimu s:tfiing TIE D h@ rc 

dloqcd io @l for % e hou.nd HCI (5 D|,, I M) M !4ted. fte orsdic lavq v6 

rcnoved on a s@@tns fiDnel ed w.sh.d {ith dichlorenethm (3 i 20 nL) Iltc 

@mbine{t ory$ic ponioN w€E wash.d with NaHCO, (5 DL, I M) and dried ovd Msso.. 

fouowd by dapoEtion ofsolvot ir velo 10 vi.ld llls 0.59 g, 98'lo vi.ld) rIl_NMf, 

(400 MHz cDcl3),: 4-84 (2H, tL 2 x CH), 3 ol (6H,s,2xoMe)' 1.79 (4H, '! 2 x cHr' 

r.43 (6H,4 h6r = 5 68a2 r cHt) 

5J.IJJ Sylltdit ol +Anlncj-boDoDy.idlr. (l l0) 

ln s tqoaFl murd bonod nsk (500 ttl.), r $lulio! of +dimplddine 

(109) (4.00 g. 42.45 mol) in @lonihil. (250 nL) B pleP@d. The 

brcmiMrins €aa.nl 1r'-brenoskcitmidc (5.66 s, 31.88 mol) @ 

Attnn nlc St tlh.tit 

slowly added and @tion flsk w wapFd in alminiu foil The Emtion nixtw w3s 

kept at @n lempdtu {or 48 hoB wiUr @ntinuou stining The sollent wa 

e!,.podcd in e@ &d i[e caidu wd stshcd with Naot(a (50 nL) Ir'e aq@u 

hixl@ M qtEr€d vilh dichlomdhe (3 x 70 mL) and l}€ @mbi'.d o4djc 

eft&ls wa diLd qs MgSO. b.fG .v.po6ri6 in l{'@ io .frord a yelow elid vfiich 

I puifi.d br 6ing sili€ s.l @llm chr@Dlognp[y (3% n {hevdicllombdlE ) 

lo afoirl @npound Ir0 (2.33 s, 32v" yicld). |H-NMR (,OO MHz, CDCL) A 8.19 (lH, s, 

Pry-H), ?.E? (1H, d,.,4.6 = 5.1 Ha Pty-rD, 5.51 0H, 4 4 i = 5 l Ilz Prv_H), 5 09 (2H h( 

s.NHr. 

NH' 

.\-.* 

tl 

t72

i3.r.2,4 

At wEi. Srnth.s6 

Sy I6i. of lBnrca{2I'5ldln.thylprmlidinyl)Dvridltu 0rr) 

4-Amim'3'bomopyridin€ (ll0) (0.90 s, 5.25 mol) !6 bken to ! 

t@mk rcurd botoD fiask (100 nL) ! dislvcd i!THF (15 nL) 

folloved by 0E ponio.-wis adcnion of N.B (6S,4 dispeed in 

ninent oil, 0.605 g. 15.?2 mol). The nixtw M stiftd for thra 

"cJ- 

#" 

ho$ ai Dbient tcmpdatw. 2s,5s-h€Mcdiol dim.lh&esutfoDL (108) (l 14 g' 4'26 

mol) M artdetl s a $lulioo in THF (15 nL) Anq rnaile for 24 hous' th€ rdtioh 

mixnE s @L4 qu@led win *ard ard dt'*Ld Mth drchlodnctbae (3 x 50 bL) 

Th. ombired orgdic mixhE I dricd os MgSOG saloELd in v&@ ald pufied 

by sili@ gel collm chtomatoShphy (lclo n.thdoudichloretuethN) ro vield @mPound 

lll (0.40 e,30% yield) s. yenow oil. |H-NMR (400 MHz cDcL)dr8.36{lH s, Prv_ 

H).8.09 (rH, d, J., r = 5 3 rL, Pry-II),5 56 (lH, d,Jt6 = 5 3 Hz Prr-A),4 27 (2H'n,2\ 

crD, 2-07 (2H, n, CHt, 1.43 (2s, o, CHr), 0.86 (6H, br s, 2 x cHt 

5.3.11.5 Syltbair of (fcycloP..trdidylnercuri. 

rcrnph.nyLtclob .di.!c).ob.!(113) 

of (r'

@ dislv.d aeait in dicuotonab!ft lxt dticd (M MgSO. Ad$aplion 6ll@ 

chsmtography M cdi€d oul dd on elution sth 100% heMe aflord'd lnc ataning 

nbl

coniimB stirins bcf@ t!'@ling tl -78 'C and ld

dopwis over tN ho6. Thc nix1E M suowd b @l for half d hou at which poini 

E|OH (15 d[) sd add.d to dilur€ th€ @rioo Ein@ follow'd bv the addidon of 2inc 

chlorid. (22.00 & 161 2 mol) Th. nirae .nd hanilg for dE hoB ar I l0 qC' *a 

qudch.d ir i@{ld *stq (l5o nL) The dixt@ vs qdacted wilh dichl@m'ths' (2 

x 300 nL} Tn€ dichlorcncthe. exrrs.t w lilta€d ald diicd ov" elvdrcu MsSOt 

fouowcd by luoval of th. elvat m a rci.ry 4'poElol For th' PuF* ofpuifidtiot'. 

@llm chrcMrogBphy *s ceied oln on sili@ gel bv stsrling with DCM/hqa* (l:l) 

d .luent. conpoud U6 (5 38, 84% vield) duied !l soe/" (DCM/hc@) rH-NMR (400 

MHa cDclr) d: 7 06 (rH. 4 r.6 = 8 8 Hz' Ar_lt) 5 91 0H' 4 I 6 = 2 4 Hl At-H)' 5 19 

(l H, dd, J67= 8.s Ha./d. = 2-4 r4 Ar'H),l ?l (3H' s, oMe),3 58 OH' s' NMc)' 2 20 

(lH, s, M.). 

53.13.2 Synlbdi!otgM.rnory'ljnb.Ovlildolh_2{nt(lr7) 

ln . rF@k

To a $lurion of KHMDS in THF (1.2 €q, -l 0 M) ar -?E 'C, s6 adtlcd a 3olulion or 

oxindol. (105) in THF (o.l M) This slldon s dlo$ld ro $n ar -7E rc' $cn 

u@fened o a $lution of chlorofomte in THF (l 2 €q, o 6 M) al -?8 "c This solution 

E allowcd to w to r! fi.n cx[&lld tud 0 l M tlcl bv Elro- Tt' @bin'd orgeic 

ponion M wash€.lwiih bnnc, dticd ovd MISO filtdEd and on@trared (rcl! v'pou) 

'IrE Eside M puified by 0s!h chmalogaPhv 

s3.13,4 

13.1.3,5 

R.pMa.iiv. Prt at.n oa $. 3!Dih6it tM'rhorv-Llai!3tlv|orindoldolorto! 

6 

Sy n6ir of 5-M.tloxyJJdir.lhvl-l/{-lndol'2-vl ph'nvl "rbotdc 

0r3r) 

A elulion of in€rhoty-l inine$vlindolin_24rc 

(rrD (0.592 s,3.10 mol) in THF (4 tiL) wa added 

slowly 1o ! $lution of KIIMDS (0-743 g, 3.72 ttml, 

Altrich) in TH! (4 mL) 6l -?8 "c The soMion @ 

snrr.d at -?8 oC for l0 min ed 6d tnlsf.d.rl 'la a cdult to a eluion of Ph€dvl 

dn@fom.le (0.4? DL, 3.?4 mol, Aldrich) in mF (5 rnl-) tl -78 "C Th' durion 96 

aUo$ed !o w@ to i! lh.n pourcd i o 0 l M HCI' drd 'xllaclld *ilh Et?O The @nbired 

orydic layes w€E wdhed with bdrc, dried ovd MgSOa, fil|ed ed @ncotrded (rola 

va!oo). Th. cid@ ws Puiticd bv flsh chromtoenPhv (sili6 g'l' 2G60 Fh) witj 

EtOAc^rM (5D5) s dF dEn! thu vi.lding thc pw U8' 6 a *tit€ cr)sullirc $lid 

(0.61 e, 6370). Analylical TLC, EloAcrEme (3/?)' R- 0 'i5 

Moleulu ion dlcula&d for CtrHDNOa:3ll-ll5q [M + H]" EI_MS foud "/' = 

2r2.1234i M. p 59il "ci IR (NaCl die, mn) l?81, c=oi ll8?, c-o; lo3?, c4; tll- 

NMR (400 MHa CDcll) dr7.4'l_719 (2H, n. Ph'H),7-33-7 25 (lH' m' Ph-H)' 7ll (lH' 

4r.! - ?.r Hz. Ar_H),5 9? 0H' 4 J..6 = 1.5 H4 Ar-tr),5-86 ( llt' u- Jir = 7 t wJ6 ' 

N 

I 

c

= 1.5 Hz, Ar'H), 3.84 (3fl, s, OM.), 3.60 (3H, s, NM.)' 2.20 (3n' 

MHz, CDCIr) r: 2 x 1546, l5l l, 139.4,2 r 130.0, 128 0' 125 8, 2 x 120.8, lll.8, I10,1, 

10t.5, 95.6, 55.3,28.8, ?-7. 

5.t.1J,6 

,lstnd.tric Syith.tit 

s, Me). rrc-NMR 0oo 

Syolhdb of l,r,r-Trt{blop}Dcrbvlprep.F2'vl 5-EOo!vn;' 

didelbyull-indol-2-yl.nbo!.t (UEb) 

By lling Uc 8Eft,al PrEed@ oudnd.borc for 

th. syoihGis of@mpoud U8h, I,l,l'Eichloo2- 

m.ihylpoFo-2-yt 5-nethoxy{,3{ineihyl_lt{' 

indol2-yl @bonale (0.6? s, 55% yicld) wa 

*€r"f,*'i", 

syoth.sircd flon @dlomd ll? (0 59 g, 3 lO md) s a ianinS nstdial in lhe ps'rce 

of 22,2ticblob_t,lnimehylethyl chloofotdatc (0893 A l72 lmol' Aldrich) 

Molcculd ion calculai!.d for c,6lirclrNol + H: 394 0379; [M + H]" C,dHrtclrNot + Na: 

415.Ol96i [M + N.]' EI-MS found st n = 394 01?9; rE-NMR (',Oo MHz, CDCIr) 

',: 

7.09 0l! d, Jr.6 - 82llz, At-lt,5 9? (ltl, d,1.6 = I J tI"- Ai_H),5 86 0H, d4 Jq? = 

E.2 H2, J6.. = l5 Hz, Ar-rD, 3.E4 (3H, s, OM.), 1.58 OH, s, NMe), 2 16 (3H' s' Mc)' l 9E 

(6H, s,2 x Me). tic-NMR 000 MHz, cDcl!) rr 2 x 154.4, 150.3, 1399. 128-0' 127 3' 

122,3, 120.6, IIl9, 95.4, 91.8, 55 2,2a 8,2 x2l 0"1 5. 

5.3,1.!.7 sy.th4B ol 5-M.lhoty-lJ-dio.thvl-ll1-indol-2-vl +.iimPh€lvl 

By siog gocnl proed@ fd llF iynthest of 

cnol c{todr6 (sedoc5l-1.33),034 s ot 

KHMDS (1.?3 mol) M added to 0.2E 8 of 

1l? (1.46 mol) in Tm (4 nL). Futh.t 

additior of+nitrophdyl clrloofomtlc (0 34 8, 170 

consi.nt llining tor % d hou atroded conDoltrd llEc (0.19 g, 

I 

*@"f,o't"-*^*" 

I 

173

yeuow sorid. |E-NMR (400 MIIZ, CDCb) r: 8.14 (2U, 4 4612r'= 

8 8 Hz' Ph'H)' ? 48 

(2H, d, Jrzr rr.= E.8 H2, Ph-rD, ?.0s (lH,4J'.6 = E 2 Ha Ar-H)' 5 98 (|H'd'i 6 = I2 

Ha Ar-H), 5.E6 (rH, d4 J6 ? = 8 2H1J6.1- t.2ll\ At'rI),3 84 (lH' s' oMc)' 3 59 (3H' 

s, NMe), 2. l9 (lH, s, Me) 

5.3.1.3.8 Sy h.rb of B.itvl_tretbotv_1J{iEetlvl_1fl-irdol2-vl c'rboo'l€ 

Usiry rhe ScFal 

(106!t) .nd $.ozvL9tuftolv-lJ.dtb'tnvtudolin-2{!' (1 lE ) 

nsthod for the sFth4tb of I lEt 

and lrEb fron 5-n.tboxr1,3{ittrdhvlin&lin-2- 

one (0.592 g, 3.10 mol) in IIIF (4 mL) in th' 

pBn@ of KHMDS (0 743 g,3 ?2 mol, Aldrich) 

in Tgr (4 mL) at -7s 'C ronoeEd bv sddition or b'lzvl chtorcfomat' (0 632 s' 3-?0 

mot), onpound 1r& (0.38 & 43"/o) sar oboin'

fittdL B @@nlritc

visoE liquid. wde obhined. fte cry3rlls wrc wdhed with hdtue fist dd lhfl wilh 

Tbe mLC on ChiElel OD afo.ded dr$sls whjch v@ Frf61 r&m.L of I l9r (vi€ld: 

,r4./t, stiL tn. mrhd liqbr @cisred of>gt% e I l9r (}1eld: 56%). 

HPIr d.b for ll9.r HPLC (chiBl@l OD,0.46 @ x 25 co. 95;05 hctudisoPrcpaml' 

lo munin) TR - t9.6 hin (nimt, Tr = 23.5 nin (@joo- An lylicll TlC, 35% 

EtoAc/hqd., fu= 0,31. Mddutd id.slcul.trC fc CrtHrrNOi 3ll ll58; [M 

+ El', 

Er-Ms found tl ',, = I t2.1230; n. p I lrt-l 16 .q rR (Nacl dis, dn) 176l, C{; I ?17, 

c{; I i 90, co; fH-NMR (400 Nfrla cl]Elt) 6:1.21-7 -21 \2H. n, Ph-H), 7.lr|'7.l0 OH, 

h, Ar-rD,5.91.5.86 (3H, n, Ph-I{),5.82 (lH, dd, J6.' = 7 8 H2,4. = l 5 H2' ArH),5 75 

(lH, d, Jx6 = 7.8 Hz, ArH), 3.75 (3tI, s, oM.), 3.21 (3H, s, NMc), 1.69 0H, s, Mc)'3c' 

NMR(l00MrACDCL)r: 1746, 168.6, 155.5, 1506, 13?.4, llr't,2x l295 t2s t 2x 

r21.4, 1t3.7, 1r0.5, 109.3, 55.1,25.9, 20.3. 

5J.1.4.0 S}!tl6!' ol (.l}l,r,1-Trt hloF2-ndnybtu9.!-t-yl $D.ato!v-l'l 

dinclhyl-2{toiodolitrcl{..horylrte (l l9b) 

A $lution of catdyst 105 (4.01 me, 0.0061 mol) in 

tolMe (5.0 nL) 6 adtled b u8b (23 ms, 0.061 

ml) in a bund botion fl6t (10 mL) onlAiniig a 

magnetic b&. And 24 h, lhc elutiotr M @@ntrded in 

)aru. Th€ crud. r.sidE w disolred in dicltloDm€lhoe dd puilied by flah .ol@ 

chrcoarognphy by uine mixnre of DCM/hdtr (95/05) io yi.ld I r9b (14 ng, 6% vi€ld, 

50'l. e)- By cluging th. el@t sys&D, diff@nr e FdG 9e obllin d (Redtt T.bL_ 

5.2,Pasel6E). 

1i "i.[.t'" 

; ccrr 

I

HPLC drl. aor llgb: HPLC (Chiralel oD, 0 46 cm i 25 cn, 98:02 hqm./ieopopdol. 

Lo nvmin) TR = 19.6 bin (mjd), Tr = 221 mh (mbor) Analrlicil dc' lov" 

EtoAc/hex$., R- 0.54- Mot4uls ion calculaLd for cr6ritrClrNol + g: 394 03?9; M + 

Hl', c,;H,rclrNo4 + Na: 415 ol96: M + Naf EI-MS foud !t n/z = 194 03?9; |H'NMR 

(am rvcq CDCL) r: J.66 (1H,4.4.6 = s: H,, Ar-I{),5 84 0H,4Ja.6= I l Hz At-to' 

512 (l:'l, d4, Jfi = 8.2 tra J6,r = I t Ha Ar-r0, l.?2 (3H, s, OM€),3 10 (lH' s, NMe)' 

l.?9 (3H, s" M.), 1.64 (3H,5. Mc), 1.58 (3H,3, Me) rrc-NMR (100 MHa cDclr) 

': 

t72.4, 765-t, 157 .2, 125.4, 115.6, I15.3, loEJ, 1082, 107 4' E7 9' 55 6' 55 4,2A2' 25A' 

20.5,18.5. 

5J.1,4.1 Sylrf,6tof(J!+Nirbpb.rtltE.lholvl,fiildnv!2{:oirdolilt3_ 

c.rboryl.b O r9c) 

A soluriod of dalyst r05 (4.5? m& 0.007 nnol) in 

totueJDCM (4/1, 5-0 mL) wc addcd lo ll& (50 

Dg, 0.14 mnol) in a roud botlom flask (10 nL) 

conidd4 ! mgnetic b{. Altq 48 b. rbe $lvdt s6 

ealrdred in @@. 'nte crudc GidE s dr$h€d in dichtodrclhe !'d Purified bv 

flsh collm chrtnatogmPby by uing t slv..( nixtN of DCMAe@ (95/05) io vi€ld 

llgc (15 m8, ?ry. yi.ld,5% e) IB-NMR (4001,fl12 cDclr) r:8-14 (2H' d' Jry16 = 

9.2 Hz, Ph'H), ?-06 (2H, d, J,{1!r - 92 Ha Ph-E),5 62 (lH, d, J'.6 - 8 4 Ha A''H)' 

t.?6(lH.d,.1.6= l 8H2, AFH),?84(lH,dd,./d,t=E4 HaJ6a= l 8 Hz'Ar_H),375 

(lH, s, oMc). 3.12 (3H, s, NMc), 1.20 (3H, q M.) 

5.1.1.41 

tIFo 

Sy tBit oa (,tlBozyl lrdhoryJ,3diDcthtl-2-oroirdolire!'

A elution of €ialyst 93 (1.5 ns, 0.0023 md) ir 

tolu€ne (4.0 oL) *6 add.d to 106d (15 ng, 0.046 t'ml) 

in a ound bot@ Aak (10 DL) mt jrng I oagle[c 

bd. Ait r 36 h, lhc elutid B @n€nlnldl n wo 

Th€ crude 6idue {a di$lv.n in dichlorcme$ee 

[o^* 

and puili.d by flah @lllm 

chrc.ralo8npiy by uins a elv€ nixlllr€ of DCM/hcre (90/10) to vieb lrgd (ll7 

ms, ?8% yi.t, svo 4). rI|-NMR (4OO MHa CDCIr) d: t28 (3H n' Ph-H)' ?-16 (2H, m' 

Ph-FI), 5.76 (lH, 4 Jr.6 = E4 Ha At-H), 5 81 0H, 4 i.6 = 2.8 Hz' Ar_H)' ? 08 0H, d4 

J6t = s.4 rrz Jr,t- 2.8 rtz Ar-tI), 5.09 (2H, s, CH),3.?2 €H' s' oMc), 1.20 Otl, s, 

NMe). 1.65 (3H, !, Mc} 

53.r.4.1 Sy.lhdlt or (5)-tM.lbo:y-ri{iD.ttyl_2{toi!dolln}3q$o!vlic 

.cid (120) 

ln a 25 nL mund bonom flaslq 4 mL eludon ofl-ior!d(0.25 

r'0 b added to !5 n8 or 119. (0.048 nml) disslvcd m 4 

mL THL Thc hixlE M k@t a1'\m &nP.nlw ot€n$r 

wilh cotut.nr sdEing. The p6ace of a bi-layq light v.uow 

""o--"{\'\o* 

t Fo 

nixr@ s @roid.i.d 6 ildicdion of &id fdrurid lt @ pouEd inio 20 eL 01 M 

HCl, and .xtd.d towi@ Biib dcbl@ndhe 'It .mbin d o4pnic latq w *lshed 

eith brire, dried ovd M8SO4 filh.d trd @n@Far.d (rcta vaPou} '['c 6id@ wa 

puifi€d by flsh chrcoatogBphy Gili6 s.1,20{0 Fn) wilh EIOAC/DCM (10,90)' 

yieldinS r20 (? m8, 63% yieltl)- Analtlical TLC, EtOAo/DCM (l/7), Rr= 0.36 'II'NMR 

(aoo MHa cDclr) ,; ?.02 (lH, d, Jr.. - 1.2 Hz, Ar'H), 5.84 (2H, oecrlaP, Ar-E). 179 

OH, i oM.), 3.14 (3H, s, NM.), | -19 OH, s, Mc).

5.4 Conclusion 

The prcsc.t $udy w.êA r\* TitusPotu .tkpa i! a nch euce of mMrtoloxic 

cl€odldc-tyle frtuoditerp.@iG ed aporyhie alkdoids ltil studv led io th€ i$l.tion 

of twnty{im *@!dary betslolilB iob I .f&Pd *hch 6 be clasifi.d 6 b.ld; 

Cl.mdxctyF dft.1Fr6 

> Nie new cLtod,tFttF fi@odit rycmrds 1-9 

> Six *nou clao

5.6 GLOSSARY 

. 'I|-NMR SlstrD: A on ni|rr@ional sFcEu poton NMR which povides 

infomdion.bod rb. clelronic mviDd4l ofthe pretons pcent in . nolaule. 

Th. sp@L.l tuge for 'E-NMR sIElrM i! r-12 pptrr. 

. Artibrcr.ri.l A chdical or dDg with a Imvd ability 10 kill b€.rcna io a 

. And{..er: A ch€ni.al subslad led !o i.Iibit the 6pid 8o*th of @cd ells 

th,r Nll i! h.ltira tbe fo@tion of d.lig@r nDoG 

. Aoli-furgd: A dtug or chedicd $.d io lElr lhe infeiio6 qed bv a nrgu 

. Adi{rld. : A sub6r.ne used lo pEv6t or slow doM thc oxidaiion pm6 in 

o4ehns !o svoid or ninimire ag.irg &d oxi.latlv. slr.s. 

. Arli{pldodis A dng or ch€hicsl suklee Nd io ll4l involut rv 

@nr&rio8 ofBBLs ald ebLd disord.B. 

. A$ry: The idtirg or m@ing lhc a.liviy of a drug d ! brdhcnical in d 

. B.frc/, Y..rt. Batr's ye61 is SMhqodttes cetevisiae, snain of ycdn ued for 

bsling &d brcwin,a. ln th. fi.ld of oiguic synth6is, it hs ben us.d for the 

*leliv. redcrior olorbonyl @mpourds, 

. D* Pqt/p.rclt pak: A Fir 

wnh I00%i s$ity in ihe ns sp6[tm whicn 

ei*s du. 10 rhe nosl rhbl. ion fom.d by th. Iiagltroladon of pell mol4ul€ in 

e ioniatiod chrmbcr. The intensitis of oth€t Fals in lhc mss speclrm e€ 

delmircd Glrtiv€ to the b.* ped( 

. Bioey: D.l.minariod of llc pocrcy of a mpl. by ils .fi.d ot living 

. Bi6ytrlb6ir: The Dule oftE fon tion ofor8qnc molecules ftoD b6ic building 

bldks in living mltd.

. Bn.d-B.rd (BB) '!C-NMR sp.carun: Pre1on (H) d@uPlcd !3C-NMR 

sp*dM. sdich pdvi&s inlotution a,lDu! the Een&@s of .il iltc @bons 

pEsl i! ! nol@le wilhoul ay @upling inr.adod. 

r Crlrlyrt: A @npoud lhl1 trldces th€ dte of. chemical E&tion while 

enaininS inracl at rh. .nd of Elction ll @ b. Eov.Gd anq lh. compl.tron of 

tb. chcbi.d @ction. 

. Ch.dlc.l Shift: In NMR, chmical shin Ef€6 to lbe difleM.. belwed the 

p@$ion frcqu.ncy ol s p6rticdd n@1.6 dd thc sigtal fo. a EfftNa I is 

d!65.d in pDn (FrB F mini@) .nd i5 EPenLd bv a slmbol a 

. CbrcDrtogr.nr 11 is a plot or detecto. signal oulput vcBs tin€ or clution volme 

duinS th. chrcmatogr.phic prcm. 

. Coluo! .nrco.lo8npby: A olum is tubltr stude 6nt ining $lid 

slalioiaty stbsl tce which is us.d for th. s.pmdon &d puification of chenical 

dtitie tom conPld mi,$@. 

. CosY-d spettur A hom@wl.{ tqoiin$ional NMR sFcLd shoMDg 

'Hl H couplincs @@lal,otu of scdinal and vicinal pbions in a nokcuL' 

. colplilg coBLlt S.dq oupliDg ! ! ltsugb-bord int tslion b'te@ nutld 

spiB- OE Mifd.rion of th. JouPling is rhe sPlitti!8 of |sM@ liB Th' 

mag.itudc ofthe splining is knoM d drc couplins @cBnr ''J' dd is lxPesed in 

ct let*cond or Hz It is ind.poddt ot lhe slrength of the.pplied hagtEtic fleld 

bur d.Fnds on |he ooleuld $ash@isrrv and dihdral 4elc b.t@n th' 

6upt.d poio6. The J vtl@ My b. .itha positivc or rc8rtiv€ in sign. 

. Crlololl.ity: C,'totoxicity i! tl| .bilily of d subtance to be loxic lo panicul& 

. DirtortiorLs Elb.trc@.tri by Pohrlz.dor Tr.!t(.. (DEPI)I 'nF muli_Pul* 

|3C-NMR.xp€im. at the &g16 ofF 45", 9o'. dd 135'to dif€r.no.t betko 

pdm.iy, s@idaty ed t tlitrycdboG.

Elcrntr lDp.ct Ma Spetnu (EI-MS): A plot of ,/z vdu itt nsitie 

@nt ilirg infonDdion abod lhe sttltfftl fdn6 thrcueh tigncnlation p$ten 

ollhe @bpouds by alplicalion of. hi8ll c!..gt elemn b.s 

. Elo.c: Tn€ dnbioaiion of mobile phe ard elure €nting fom a colMn, 

. Eludt Mobit. phe ed to elur. [F smpt. Gon a cdlm in order 10 achid' 

. El io!: The pDes ofpasbg a mobilc PtN tlsu€l lhe colum 1o s€pt ur. $c 

. rrt AroD BoDb.ldrdr Ms sp€fio (FABMS)| The eft ionianon 

ralniq@ Gcd in l|rN {eeooctry !o l@le rh€ tuldlrt ion pet for thc 

.letermiBlion of hotddd fodul& 

. Flo* r.ler Th€ volmebic tlow of mobile ph4e Fr uii tiDe threud s LC 

. Gndi. .luiiolr Ah.thodofchotulogEpbics.pistionbyqhichrhepol&ilv 

ofthe nobile phe idltas gEdully to dc.@ lhe Fpdho! tme 

. H.temrrcl€or Mlhiple Bood Coo!.ctivity (HMBC): 11 is e inv€N 

h.r€rclet@ t*o{in€aioMl NMR t{hliqw Itr th4. €xp.rin€fis' $e 

Msr.rizdon of'iC relei is d.t4r.d thtuugh lhe 'H n@Li i! ordd lo ill.lle 

sitiiitt of sigD,ts. Iris lehniqE is t!.d lo iMsiiert th. l6g-tu9c, 

hetcmucteE inlcFclioN bcts@ qbo6 dd Fotom 

(up 1o fou-bonds). 

. Il€trcNcL.r Multipl€ Qortlo Coh.relc. (HMQC): lt is e int.s 

hcrronucla twcdim4ional NMR l6hDqrc dploy.d b anallish lhe didl 

Iw'rc oFbond shrn mla|jN. ln lhs cxFindr th. rrc nwlc' ffi d.kted 

orcudr th€t .lTols on |lr Nlei. 

. gtgb-solutior ELclrcn Impr.t Met SpetruD (HRf,I'MS). A melhod of 

crer |rc m4wbcnts for diet d.Lminalion of cl.m€ al @mposirio.. A 

doude f@cing 

'6 Sdlob.r.. is !@tlly r€qlired io ldd tle HREI-MS.

. gPlcr Liquid €brcmlogEphic t4hriq* u$d for the *pdslion of sdple 

mixtuF uder lhe infle@ of hid pF$G ai coNlar* floq 6& 

. IDDlloDodnLton A sub3la&. thsr i.nllEIB de im@ svst@ or d 

. Infnr.rt spatm.opy 0R): Th. tehniqE usd ro determinc th. fucri@aliri€s 

F6e in a nol€cd.- Infrted sFcln d. prod@€d by de absrpdon of inrni.d 

ndialions (350"4200 cn r) by orBdic not6ul.s 

. r,-vitu: T}G dFri|rrfu do.. outsid. dc bod, of I'qng orSrnistu 

. rrriD: Th. dFibdts dom within d. body ol Lug orgaisd 

. I'dnti.: A @nsldr @nposidon of mobile Ph4 u.d in liqlid chDaiogmPhv 

. Mobile phs.t 'Ite solvmvea th.t mov6 ihe solutes tlmuS! 3 @lue 

. MolerLr lob (Lf): TIE ion forn d fren lt nolculc by lo$ of onlv one 

€lelron. Thc ,t/2 6tio of dE mleuld ior gi6 thc mleule wigl of the 

. Nmler Ovcrhrrrr E rmen.nl Difrer.ns Spetrrn (NOE): Ir tu a lD 

NMR .xFrin .t ued to tletemine ilE steFchoistry of oigmic holtrules wilb 

th€ help of signal cnlrn dent @Ed by ditDld couplins of nul.i iD Ptuxinitv. 

. N!.ldr ov.rh.Br E!l!.ad Spetrcpt (NoFAD. Th.2D v6ion or 

NOE us{d lo d.ldnirc tb€ st t@bdisEy of mled€ wilh thc hclp of i etuting 

. N{cl@pbile A Eage thal foms ach@ical bood by donaling a pair of.Lctroro 

|o o el€crrophile duing chmical G&tion. 

. ocbddylrl.!. {ODS): Modificd rili€ e.l by anehrdt of @1ad@vl dton_ 

chain lo silio It ir trs.d a .derbcnr i. HPLC. 

. Optlql Rotrti.n: h is th€ phyricd pbP.lg ofth€ ontoud 10 olale th€ plde of 

polri-d light, €ilhd cl@kwis or @@krcl6kwise.

Org.non.t Uic: Orgdic ohpoo!& onlainine @bonG) diBdv lintcd lo 

R..mE.D.!i. A clN of oe.nic Eetios qt@ th. clton fm. wo* 

udergod skelctd ch.ags wilhoul 8!in 

or lca ofdy aid'/Srottp 

R.rado! Ti[. (Td: Irr tid. ditrtu b.tv6 th. iljdtion dd pe* 

hdin@ of r enain sple, It cFenls lh€ linc rako bv dLin Dol6'ne b 

pN lhmugh tlE whoL l6gln of th. 6lum. 

Rw€red-ph.t. Cbrcrotogn y: A liquid .hromtogaPhh iechniqrc thal us.s 

a mn-Dola( sLtion ry phc sd . pold nobile phse lt is th. mosl onmon 

n lhod of $p..lliotr in HPLC. 

S..|Mh.uhri : Il Ff6 ro a tbrc dincGio."l sfuEcDots of alomggmup6 in 

St rugeEi. C.!L./.hir.l.ot n Any poini in a moland. b.ebg gmups swh 

lh,r e inierchonS. of dy tm erc|4s ehich ldd to sr.@ison6 

Tli!-Lryer ChrcorogEpny GLC): A qualit tiflq@litdive m'lhod of 

smple eaiysis u*d 10 seps4t mixtuts Ttunlarti ctuonabgralhv cd Dc 

enplord on aluninM Ioil, Clds plar. or platic shel with a @aled adsotb'fi' 

TLC @ be dev.lop.d i! a lank @ rining a $|vdr nilt4. Th. ompon€nr3 in a 

spL dovc vilh dif.mr llo* 6tc (&) by ltt €pi[ai, .cton agttsl gaviq 

Ultdiol.l Sp4thE (u9r It is a ptot of mv€ lengih of ulraviolet ndiatios vr 

abetb&@. TIF absorption spetfliD (Uv sFctru) of u o€dic compoud s 

prcet d in a gnph of e or log ..gtiBt *av.Lnstbs .xpEsd in nmn'lct 

l9u

5.7 List of Abbreviations 

rtoNMR-_ 

ID 

rtjNnR 

,D- 

^;i- 

c 

;- 

-cts 

cc 

ait6D 

Fradot pll,s. (cbre;doSF phv @llm !6cki'8) 

=1 

cDcl, -l 

cosY 

dl 

DBE 

DCM 

DEPT 

DIBAI- 

DMSO 

dd$l.t I 

double bond .quivalo!! 

di{orrionl*r ..hecdcnl by pordz.non |rdsM 

dii$bdyl.l6irim hy.Li& 

t9!

EI 

Er-i,{s- 

Ert|r 

FAB 

Fis. 

H 

HMBC 

cl6mn imp&t ioiarion 

€l{fon i6pal nB lpet nE Y 

h.r.M$ld m lipl. bonl @cLlion lp€clrwopy 

HMG-CoA ]-hldoxy-l-m.thylglut ryl4oA 

HMQC heltund@ miiplc q@n!n @lE|!@ 

HPT,c 

HR 

HREI-MS 

high Frfomn .r'Fg3e l4oil.h@dogEphy 

bigh lgnrid d.dton inF.r ds sP..turdy 

t{Ts hiC dmlghed*|Eo'g 

llz 

tc 

Ics IElf Mind irhibitory @Mcntltion 

INADEQUATE iM€dible natunl aludr@ doublc quitn FeNf€r .rpdimdl 

IR 

KBr 

L 

It 

LC.MS fquid cirmlog4hy EBi 3p.crroo.ry 

taMs-Ms liquid clrnolrogr9hy t ttdd 'a sFctbo.t_y 

LC.NMR liquid chmdogryhy nulo ffglctic E3)@ 

l 

t94

M.OH 

Mtlz 

MS 

N!.So. 

milliliGr 

NAD rilrituiL o&rir. di lolid. 

NBS 

rBuLi 

rBUOH 

n8 

NMR nEI... n gndic @mcc 

NOE nuhe Ovcrttr|g effecl 

NOESY nul.a Ov€rhlM arl|lMncnt sp.

N 

ROESY 

RP 

RT 

SN 

-siE 

rot fng t@ Otqrblg ccIIrE q6t6spY 

ffi- 

$*tu"-Gffi 

6itd pt"- "txr"6; 

Tlc 

Tta lhin Lrys chrEeSr4hY 

tocsY br.t @ftbrid lpccr@Py 

vLc }!r'M lhuid .lmalog4hy 

ZnCt2 

;- 

bct 

t d.lti, ctmicd dnn b Fi! Dq dni@ (!!d) 

--l 

196

5.7 List of Publications 

l. 

,kt"flttctic qatly.ttt { otttt&b.t catclntta c qdsw, tt r.og.re @&. tt 

dA& o/Ce44 l@'otqt,a ltrr.d l!.4 gsv v. Nsrylt' 

C@iEy lt d.*o, li.Liid Xedt !d frid?tr I Rldrd+ Ltdndn 

ltt'',!i,r,5463X2434. 

qr4nter.gp. @.tP.de !1''' nowra qiPa M lqt'l 

Chrtuy, Xrr..r.d lE4 Khnt|L Stlti' Ah.d Attd-' Soir A 

s,er.No.dirE lji.d Art}s{&d, J rh ltad' ($ttoin d} 

Ittd@ c.'ttda/.,tt tod n'l,sp

nuhammad lsmall

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