Name: 4137-56-8|((3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 4-methylbenzenesulfonate|98+%
Brand: Ambeed
SKU: A583457
Rating: 96 (29 reviews)

1
[ 4137-56-8 ]
[ 38838-06-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium iodide In N,N-dimethyl-formamide; toluene for 2h; Reflux;	3 Example 3 Preparation of Compound III 359 g of Compound II, 300.8 g of NaI, 1330 ml of toluene and 332 ml of DMF were added to a 3000 ml three-necked flask, and the mixture was heated to reflux with stirring to maintain a refluxing reaction for 2 hours. The reaction solution was washed successively with water (500 ml x 2) and saturated brine (500 ml x 2), dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure to give a pale yellow oil, & yield; 98%, purity 99.3%.
97%	With sodium iodide In acetone for 4h; Heating;
90%	With sodium iodide In N,N-dimethyl-formamide for 0.666667h; Heating;

	With acetone; sodium iodide
	With sodium iodide In N,N-dimethyl-formamide

Reference： [1]Current Patent Assignee: CHONGQING SHENGHUAXI PHARMACEUTICALS CO LTD; CHONGQING HUIZHI PHARMACEUTICAL RES INST - CN106279095, 2017, A Location in patent: Paragraph 0020; 0043
[2]Kobori, Yoshihiro; Myles, David C.; Whitesides, George M. [Journal of Organic Chemistry, 1992, vol. 57, # 22, p. 5899 - 5907]
[3]Abdel-Rahman, Adel A.-H.; Abdel-Megied, Ahmed E.-S.; Goda, Adel E.-S.; Zeid, Ibrahim F.; El Ashry, El Sayed H. [Nucleosides, nucleotides and nucleic acids, 2003, vol. 22, # 11, p. 2027 - 2038]
[4]Shunk et al. [Journal of the American Chemical Society, 1955, vol. 77, p. 2210] Levene; Stiller [Journal of Biological Chemistry, 1934, vol. 106, p. 421,423, 428]
[5]Araki, Younosuke; Endo, Tadatoshi; Tanji, Masaki; Arai, Yoshifusa; Ishido, Yoshiharu [Tetrahedron Letters, 1988, vol. 29, # 19, p. 2335 - 2338]

2
[ 4099-85-8 ]
[ 98-59-9 ]
[ 4137-56-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With pyridine for 3h;
97%	With pyridine at 0℃; for 2h;
91%	With pyridine at 20℃;

90%	With pyridine; dmap at 20℃; Inert atmosphere; Cooling with ice;
90%	With pyridine at 20℃; for 2h; Inert atmosphere;
90%	With dmap In pyridine at 0 - 25℃; for 5h; Inert atmosphere;	3.3. 1-O-methyl-2,3-O-isopropylidene-5-O-p-toluenesulfonyl-b-Dribofuranose(3) To a solution of 1-O-methyl-2,3-O-isopropylidene-b-D-ribofuranose(4.5 g, 0.022 mol) in dry pyridine (8.5 mL), externally cooledwith ice, was added p-toluenesulfonyl chloride (5.3 g, 0.027 mol)and catalytic amount of DMAP. The reaction mixture was stirred atroom temperature under nitrogen atmosphere for 5 h. After thistime, 2mL of distilledwaterwas added and the stirringwas kept formore 30 min. This mixture was extracted with chloroform (3 x 25mL) and the combined organic phases was washed with aqueoussolution of CuSO4 (10% w/v), saturated solution of NaHCO3, waterand dried over anhydrous sodium sulfate. Removal of the solventunder reduced pressure furnished product (3) as a white powder(90%, 7.09 g) with m.p. 85-86 °C. FT-IR n(cm1): 1358 and 1180; 1HNMR (CDCl3, 600 MHz) δ 1.29 (s, 3H, CH3), 1.45 (s, 3H, CH3), 2.46 (s,3H, CH3-aryl), 3.24 (3H, s, OCH3), 4.02 (dd, J 1.5 and 7.5 Hz, 2H, H-5 and H-50), 4.31 (ddd, J 0.6, 6.9 and 7.2 Hz, 1H, H-4), 4.53 (d,J 6.0 Hz, 1H, H-2), 4.60 (dd, J 0.3 and 5.7 Hz, 1H, H-3), 4.93 (s, 1H,H-1), 7.36 (dd, J 0.3 and 8.7 Hz, 2H, H-30), 7.81 (dd, J 0.6 and8.7 Hz, 2H, H-2’); 13C NMR (CDCl3, 150 MHz) δ 21.5, 24.7, 26.2, 54.9,69.1, 81.2, 83.4, 84.7, 109.3, 112.6, 127.8, 129.8, 132.6, 144.9. GC/MS(EI, 70 eV): 343 (M 15, 100%).
89%	With pyridine In dichloromethane
86%	With pyridine; dmap at 20℃; for 2h; Inert atmosphere; Cooling with ice;	Methyl 2,3-O-isopropylidene-5-O-p-toluenesulfonyl-b-D-ribofuranoside (10) To a solution of 8 (1.00 g, 4.90mmol) in dry pyridine (5mL) externally cooledwith an ice bath were added p-toluenesulfonyl chloride (3.00 g, 15.75mmol)and a catalytic amount of DMAP. The reaction mixture was stirred at rt undera nitrogen atmosphere for two h. After this time, 2mL of distilled water wasadded, and the stirring was kept for an additional 30 min. This mixture wasextracted with chloroform (325mL) and the combined organic phases werewashed with aqueous HCl solution (10% v/v), aqueous CuSO4 solution (10%w/v), cold water, saturated NaHCO3 solution, cold water, and dried over anhydroussodium sulfate. Removal of the solvent under reduced pressure furnisheda white powder (86%, 1.51 g) with m.p. 85-86 C (lit. 84-85 C). Rf 0.40(hexane/ethyl acetate: 7/3); IR (KBr pellet) m(cm1): 1596 (Ph), 1359 (SO2) and1180 (SO2). 1H NMR (CDCl3, 400.13MHz): d 1.29 (s, 3H, CH3), 1.45 (s, 3H,CH3), 2.46 (s, 3H, CH3-aryl), 3.23 (3H, s, OCH3), 4.01 (d, 1H, J5a,5b 2.0Hz,H-5), 4.02 (d, 1H, J5a,5b 2.0Hz, H-5) , 4.31 (t, 1H, J4,5 7.2Hz, H-4), 4.53 (d,1H, J2,3 5.9Hz, H-2), 4.60 (d, 1H, J3,2 5.9Hz, H-3), 4.93 (s, 1H, H-1), 7.36(d, 2H, J30,20 8.2Hz, H-30), 7.81 (dd, 2H, J20,30 8.2Hz, H-20). 13C NMR(CDCl3, 100.61MHz): d 21.8 (CH3-aryl), 25.1 and 26.5 (2 x CH3), 55.2(OCH3), 69.4 (C-5), 81.6 (C-3), 83.8 (C- 4), 85.1 (C-2), 109.7 (C-1), 112.9(C-6), 128.2 (C-20), 130.1 (C-30), 133.0 (C-40), 145.3 (C-10). These data are inagreement with that in the literature.[5a]
85%	In pyridine; dichloromethane Ambient temperature;
83%	With pyridine at 0℃; for 2h;
82%	With pyridine at 0 - 20℃; for 12h; Inert atmosphere;	General procedure for synthesis of tosyl-sugars (2a-e) General procedure: The stirring solutions of compounds 1a-e in pyridine at 0 °C were added with p-toluene sulphonyl chloride under anhydrous condition. The reactions was allowed to come at room temperature and further stirred for 12 h. After completion (monitered by TLC), the reaction mixtures were in vacuo concentrated and the crude obtained were purified by flash column chromatography to afford tosyl-sugars 2a-e in good yields.
81%	With pyridine; dmap at 20℃; for 5h; Cooling with ice; Inert atmosphere;
80%	With pyridine at 20℃;
80%	With pyridine at 20℃; for 20h;
76%	With pyridine Further stages;
72.86%	With pyridine In dichloromethane at 0 - 5℃; for 20h;	1 Methyl-2,3-O-isopropylidene-5-O-tosyl-β-D-ribofuranoside (2) Methyl-2,3-O-isopropylidene-5-O-tosyl-β-D-ribofuranoside (2) To a cold solution containing Methyl-2,3-O-isopropylidene-β-D-ribofuranoside (1) (108.4g, 531mmol) in CH2Cl2 (1000ml) dropwise adding 300ml of toluene-4-sulfonyl chloride (140g, 734mmol) in anhydrous pyridine solution. With vigorous stirring, the reaction was carried out at 0-5°C for 20 h. The resulting solution was washed with NaHCO3 aqueous solution, brine and evaporated to yield a syrupy mass (185g, 97.2%), which can be further crystallized from hexane and dried under high vacuum to give pure methyl-2,3-O-isopropylidene-5-O-tosyl-β-D-ribofuranoside (138.8g, 72.86% yield) as a white solid crystals. 1H NMR (CDCl3): δ1.28 and 1.45 (2s, each 3H, CMe2), 2.46 (s, 3H, aromatic Me), 3.24 (s, 3H, -OMe), 4.01 (d, 2H, J=7.2Hz, H-5), 4.31 (dt, 1H, J=7.3Hz, H-4), 4.53 (d, 1H, J=6.0Hz, H-2), 4.60(dd, 1H, J=5.6Hz, H-3), 4.93 (s, 1H, H-1), 7.36 (d, 1H, J=8.0Hz, aromatic H), 7.81 (d, 2H, J=8.2Hz, aromatic H).
70%	Stage #1: ((3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol With pyridine In dichloromethane at 0℃; for 0.166667h; Stage #2: p-toluenesulfonyl chloride In dichloromethane at 20℃; for 24h;
	With pyridine at 0℃;	Methyl 2,3-O-isopropyliden-5-O-tosyl-β-D-ribofuranoside (6); A solution of methyl 2,3-O-isopropyliden-β-D-ribofuranoside (5; 22,6 g, 0,11 mol) in pyridine (25 mL) cooled at 0°C was treated with tosyl chloride (31,6 g, 0,17 mol) added in 4 similar parts. The reaction mixture was stirred for 3,5 hours at 0°C. Then it was poured into a mixture of 250 g of ice and 250 g of water. The ice was let to melt by stirring and the mixture was filtered. The filtrate was washed with cold water (2 x 100 mL) and it was dried with the desiccator. The compound 6 was obtained as a white crystalline solid (35,6 g, 89% yield starting from d-ribose) 1H RMN (CDCl3, 500 MHz) δ 1.29 (s, 3H, CCH3), 1.45 (s, 3H, CCH3), 2.46 (s, 3H, PhCH3), 3.23 (OCH3), 4.00 (dd, J = 10.0, 6.8 Hz, 1H, H-5'a), 4.03 (dd, J = 9.9, 7.6 Hz, 1H, H-5'b), 4.31 (t, J = 7.2 Hz, 1H), 4.53 (d, J = 5.9 Hz, 1H), 4.60 (d, J = 5.9 Hz, 1H), 7.36 (d, J = 8.1 Hz, 2H, H-3"), 7.81 (d, J = 8.3 Hz, 2H, H-2").
0.984 g	With pyridine at 0 - 20℃; for 26h; Inert atmosphere;	1-O-methyl-2,3-O-isopropylidene-5-O-(p-toluenesulfonyl)-β-D-ribofuranoside (8d) Compound8d was prepared from protectedribose derivative 5 according toliterature procedures.3 Toluenesulfonyl chloride (1.413 g, 7.414mmol) was added to a stirred solution of the protected ribose derivative 5 (0.757 g, 3.707 mmol) in pyridine (8mL) at 0 °C. The reactiongradually came to RT while stirring for 26 hours. Monitoring by TLC (1:1 EtOAc/hexanes)revealed no visible starting material remaining, and the pyridine was co-evaporatedwith three portions of toluene (8 mL) by rotary evaporation. The crude product was taken up in EtOAc (60mL), washed with two portions of saturated aqueous NaHCO3 (25 mL),and one portion of brine (25 mL). Theorganic layer was dried over MgSO4, filtered, and solvent wasremoved by rotary evaporation. Productisolated as fibrous white crystals after recrystallization from hot ethanol (0.984g, 2.745 mmol, 74%).
	With pyridine
666g	With pyridine In dichloromethane at 0 - 20℃; for 5.5h;	2 Example 2 Preparation of Compound II To a 2000 ml three-necked flask was added 426 g of Compound I,342 ml of pyridine,Salt ice water bath cooling to below 0 ,A solution of p-toluenesulfonyl chloride in dichloromethane (422 g: 933 ml) was added dropwise,About 30min drop finished.The three-necked flask was then moved to room temperature,After stirring for 5 h, 311 ml of water was added dropwise,After stirring for an additional 30 min, the reaction system was transferred to a 2000 ml separatory funnel,Taking organic layer,Vacuum distillation to dryness,To obtain 732 g of the crude product of the beige solid compound II,Yield 98%. The crude product of compound II was placed in 2928ml (4V) of ethanol, stirred and heated to reflux, completely dissolved, and decolorized with 60g activated charcoal for 15min, filtered, cooled, crystallized, filtered and dried to obtain 666g of Compound II %).
	With pyridine at 25℃;
952 g	With dmap; sodium hydroxide In toluene at 5 - 15℃;	2 Example 2: Preparation of a compound of formula 2 Toluene solution of the compound of the formula 1 obtained in Example 1 and 4-dimethylaminopyridine (0.3 g) were sequentially added to a four-necked flask.Sodium hydroxide (195.0g), control temperature 5~15 °C,A solution of p-toluenesulfonyl chloride (560.0 g) in toluene (600 g) was added dropwise.After the addition is completed, the temperature control reaction is 1 to 5 hours.After TLC monitors the reaction, add water (2kg), dispense,The aqueous phase was extracted once with toluene (1.0 kg).The organic phase was combined and washed once with saturated brine (2 kg).The organic layer was concentrated, and then ethanol (2.5 kg) was added to raise the temperature to 60-75 ° C.After dissolution, the temperature was lowered to 0 to 10 °C. filter,The filter cake is rinsed once with ethanol.The blast was dried to give a white solid compound 2 952.0 g,The total yield of the two steps is 79.8%.The HPLC purity was 99.8%.
	With pyridine at 0 - 5℃; for 16h;

Reference： [1]Sarabia-Garcia, Francisco; Lopez-Herrera, F. Jorge [Tetrahedron, 1996, vol. 52, # 13, p. 4757 - 4768]
[2]Li, Xiang-Guo; Dall'Angelo, Sergio; Schweiger, Lutz F.; Zanda, Matteo; O'Hagan, David [Chemical Communications, 2012, vol. 48, # 43, p. 5247 - 5249]
[3]Wang, Guangyi; Tam, Robert C.; Gunic, Esmir; Du, Jinfa; Bard, Josie; Pai, Bharati [Journal of Medicinal Chemistry, 2000, vol. 43, # 13, p. 2566 - 2574]
[4]Ferreira, Sabrinab; Sodero, Ana C. R.; Cardoso, Mariana F. C.; Lima, Emerson S.; Kaiser, Carlos R.; Silva Jr., Floriano P.; Ferreira, Vitor F. [Journal of Medicinal Chemistry, 2010, vol. 53, # 6, p. 2364 - 2375]
[5]Downey, A. Michael; Pohl, Radek; Roithová, Jana; Hocek, Michal [Chemistry - A European Journal, 2017, vol. 23, # 16, p. 3910 - 3917]
[6]Burtsev, Ivan D.; Volov, Alexander N. [Journal of Organometallic Chemistry, 2020, vol. 922]
[7]Sairam, Pothukuchi; Puranik, Ramachandra; Sreenivasa Rao, Bhatraju; Veerabhadra Swamy, Ponnapalli; Chandra, Sharad [Carbohydrate Research, 2003, vol. 338, # 4, p. 303 - 306]
[8]Evangelista, Tereza Cristina Santos; Aquino, Gabriel Alves Souto de; Donza, Marcio Roberto H.; Leitão, Rafael Lisboa; Carvalho, Victor Salarolli de; Kaiser, Carlos Roland; Ferreira, Sabrina Baptista [Journal of Carbohydrate Chemistry, 2021, vol. 40, # 5, p. 243 - 268]
[9]Snyder. Joseph R.; Serianni, Anthony S. [Carbohydrate Research, 1987, vol. 163, p. 169 - 188]
[10]Jopp, Stefan; Komabayashi, Mirai; Stiller, Tanja [Journal of Molecular Liquids, 2021, vol. 325]
[11]Kumar, Dhananjay; Mishra, Kunj B.; Mishra, Bhuwan B.; Mondal, Saheli; Tiwari, Vinod K. [Steroids, 2014, vol. 80, p. 71 - 79]
[12]Moreau, Christelle; Kirchberger, Tanja; Swarbrick, Joanna M.; Bartlett, Stephen J.; Fliegert, Ralf; Yorgan, Timur; Bauche, Andreas; Harneit, Angelika; Guse, Andreas H.; Potter, Barry V. L. [Journal of Medicinal Chemistry, 2013, vol. 56, # 24, p. 10079 - 10102]
[13]Abdel-Rahman, Adel A.-H.; Abdel-Megied, Ahmed E.-S.; Goda, Adel E.-S.; Zeid, Ibrahim F.; El Ashry, El Sayed H. [Nucleosides, nucleotides and nucleic acids, 2003, vol. 22, # 11, p. 2027 - 2038]
[14]Ivanova; Valiullina; Shitikova; Miftakhov [Russian Journal of Organic Chemistry, 2007, vol. 43, # 5, p. 742 - 746]
[15]Župančić, Nataša; Ban, Željka; Matić, Josipa; Saftić, Dijana; Glavaš-Obrovac, Ljubica; Žinić, Biserka [Croatica Chemica Acta, 2015, vol. 88, # 1, p. 43 - 52]
[16]Current Patent Assignee: NANOMED HOLDINGS - EP2393472, 2019, B1 Location in patent: Paragraph 0142; 0145; 0146
[17]Ler, Geraldine J. M.; Xu, Weijun; Mak, Jeffrey Y. W.; Liu, Ligong; Bernhardt, Paul V.; Fairlie, David P. [Chemistry - A European Journal, 2019, vol. 25, # 68, p. 15594 - 15608]
[18]Current Patent Assignee: COLL FARMA S L; RICHMOND COM IND Y FINANCIE - EP2241556, 2010, A1 Location in patent: Page/Page column 8
[19]Bolitho, Megan E.; Corcoran, Brendan J.; Showell-Rouse, Emily I.; Wang, Keeshia Q. [Carbohydrate Research, 2014, vol. 394, p. 32 - 38]
[20]Chaves, Joana Darc Souza; Damasceno, Jaqueline Lopes; Paula, Marcela Cristina Ferreira; De Oliveira, Pollyanna Francielli; Azevedo, Gustavo Chevitarese; Matos, Renato Camargo; Lourenço, Maria Cristina S.; Tavares, Denise Crispim; Silva, Heveline; Fontes, Ana Paula Soares; De Almeida, Mauro Vieira [BioMetals, 2015, vol. 28, # 5, p. 845 - 860] Campos, Vinicius R.; Cunha, Anna C.; Silva, Wanderson A.; Ferreira, Vitor F.; Santos De Sousa, Carla; Fernandes, Patrícia D.; Moreira, Vinícius N.; Da Rocha, David R.; Dias, Flaviana R. F.; Montenegro, Raquel C.; De Souza, Maria C. B. V.; Boechat, Fernanda Da C. S.; Franco, Caroline F. J.; Resende, Jackson A. L. C. [RSC Advances, 2015, vol. 5, # 116, p. 96222 - 96229]
[21]Current Patent Assignee: CHONGQING SHENGHUAXI PHARMACEUTICALS CO LTD; CHONGQING HUIZHI PHARMACEUTICAL RES INST - CN106279095, 2017, A Location in patent: Paragraph 0018; 0041; 0042
[22]Dias, Flaviana R.F.; Novais, Juliana S.; Devillart, Talita A. do Nascimento Santos; da Silva, Wanderson Amaral; Ferreira, Matheus O.; Loureiro, Raquel de S.; Campos, Vinícius R.; Ferreira, Vitor F.; de Souza, Maria C.B.V.; Castro, Helena C.; Cunha, Anna C. [European Journal of Medicinal Chemistry, 2018, vol. 156, p. 1 - 12]
[23]Current Patent Assignee: GUANG AN KINGDAY PHARMA CHEM - CN109369736, 2019, A Location in patent: Paragraph 0046; 0047; 0048
[24]Ślusarz, Rafał; Chojnacki, Jarosław; Dmochowska, Barbara; Madaj, Janusz; Samaszko-Fiertek, Justyna [Molecules, 2020, vol. 25, # 9]

3
[ 1666-13-3 ]
[ 4137-56-8 ]
[ 86520-87-8 ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium tetrahydroborate In ethanol for 3.5h; Heating;

Reference： [1]Boullais, C.; Zylber, N.; Zylber, J.; Guilhem, J.; Gaudemer, A. [Tetrahedron, 1983, vol. 39, # 5, p. 759 - 766]

4
[ 333-20-0 ]
[ 4137-56-8 ]
[ 158420-07-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	In N,N-dimethyl-formamide at 120 - 130℃; for 6h;

Reference： [1]Pakulski, Zbigniew; Pierozynski, Donat; Zamojski, Aleksander [Tetrahedron, 1994, vol. 50, # 9, p. 2975 - 2992]

5
[ 4137-56-8 ]
[ 66-22-8 ]
[ 55221-59-5 ]

Yield	Reaction Conditions	Operation in experiment
37%	Stage #1: uracil With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20 - 80℃; for 1.5h; Stage #2: methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside In N,N-dimethyl-formamide; mineral oil at 20 - 100℃; for 20h;	General Procedures for the Preparation of ReversedNucleosides 7-11 General procedure: The sodium salt of base was prepared by stirring a suspension of an equimolar amount of the pyrimidine base 4-6 (1 mmol) and sodium hydride (50 % in oil suspension,1 mmol) in DMF (3-4 mL/mmol) at room temperature for 1 h and warming at 60-80 °C for 0.5 h. A solution of the methyl 2,3-O-isopropylidene-5-O-ptoluenesulfonyl-β-D-ribofuranoside (3) (0.8 mmol) in DMF (1.7 mL/mmol of sugar) was added dropwise to this suspension at room temperature. The reaction mixture was stirred and heated at 100 °C for 20 hours. The resulting clear solution was evaporated and the residue was dissolved in hot chloroform. The suspension was filtered through Celite and filtrate was washed with water, dried over Na2SO4 and evaporated.
	With sodium hydride 1) DMF; Yield given. Multistep reaction;

Reference： [1]Župančić, Nataša; Ban, Željka; Matić, Josipa; Saftić, Dijana; Glavaš-Obrovac, Ljubica; Žinić, Biserka [Croatica Chemica Acta, 2015, vol. 88, # 1, p. 43 - 52]
[2]Kasnar, Biserka; Skaric, Vinko; Klaic, Branimir; Zinic, Mladen [Tetrahedron Letters, 1993, vol. 34, # 31, p. 4997 - 5000]

6
[ 4137-56-8 ]
[ 62819-24-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium azide In N,N-dimethyl-formamide at 120℃; for 12h;
95%	With sodium azide In N,N-dimethyl-formamide at 120℃; for 12h;	3.4. 1-O-methyl-5-azido-5-deoxy-2,3-O-isopropylidene-b-Dribofuranose(4) To a solution 1-O-methyl-2,3-O-isopropylidene-5-O-p-toluenesulfonyl-b-D-ribofuranose (700 mg, 2.48 mmol) in dry DMF (7 mL)was added sodium azide (1.96 g, 30.15 mmol). The mixture washeated at 120 °C for 12 h and monitored by TLC (hexane/ethyl acetate7:3 and GC/MS). After cooling, acetone (10 mL) was added tothis mixture and then filtrated under vacuum. The solvent wasremoved under reduced pressure furnishing an oil that was dissolved50 mL of chloroform and washed with water (50 mL),saturated solution of NaHCO3 (50 mL) and water (50 mL). Theresulting solution was dried with anhydrous sodium sulfate, filtrated and evaporated furnishing a product (4) as yellow liquid(95%, 540 mg). IR ν(cm1): 2113 and 1377; 1H NMR (CDCl3,600 MHz) δ 1.31 (d, J 0.6 Hz, 3H, CH3), 1.47 (d, J 0.6 Hz, 3H, CH3),3.32 (s, 3H, OCH3), 3.45 (dd, J 10.9 and 5.9 Hz, 1H, H-5’), 3.54 (dd,J 10.9 and 5.9 Hz, 1H, H-5), 4.30 (td, J 5.9 and 0.6 Hz, 1H, H-4),4.59 (dd, J 5.9 and 0.6 Hz, 1H, H-2), 4.72 (dd, J 5.9 and 0.6 Hz, 1H,H-3), 4.97 (s, 1H, H-1); 13C NMR (CDCl3, 150 MHz) δ 24.8, 26.3, 55.1,53.7, 81.9, 85.0, 85.3, 109.7, 112.6. GC/MS (EI, 70 eV): 214 (M 15,100%).
91%	With sodium azide In N,N-dimethyl-formamide at 120℃; for 16h;

86%	With DEAHN₃ In N,N-dimethyl-formamide at 60℃; for 16h;
85%	With sodium azide In N,N-dimethyl-formamide at 80℃; for 18h; Inert atmosphere;	General procedure for synthesis of sugar azides (3a-j) The stirring solutions of compounds 2a-j in dry DMF were treated with NaN3 [45-52]. The reaction mixtures were further heated at 80 °C under anhydrous condition followed by constant stirring over night. After completion of reaction (monitored by TLC), the reaction mixtures were in vacuo concentrated followed by silica gel column chromatography to afford compounds 3a-j in good yields.
85%	With sodium azide In N,N-dimethyl-formamide at 120℃; for 12h;	Methyl 5-azido-5-deoxy-2,3-O-isopropylidene-b-D-ribofuranoside (11) To a solution of 10 (1.00 g, 2.79 mmol) in dry DMF (4 mL) was addedsodium azide (0.91 g, 13.97 mmol). The mixture was heated at 120 C for 12 h and monitored with TLC (hexane/ethyl acetate: 7/3). After reactionwas completed, the mixture was cooled, and acetone (10 mL) was addedand then filtered. The solvent was removed under reduced pressure furnishingan oil that was dissolved in 30mL of chloroform and washed withwater (30 mL), saturated NaHCO3 solution (30 mL), and water (30 mL).The resulting solution was dried with anhydrous sodium sulfate, filtered,and concentrated, furnishing a yellow liquid (0.54 g) in an 85% yield. Rf 0.58 (hexane/ethyl acetate: 7/3); IR (film, CHCl3) m (cm1): 2103.99 (N3)and 1382.73 (methyl isopropyl group). 1H NMR (CDCl3, 500.13 MHz): d1.32 (s, 3H, CH3), 1.49 (s, 3H, CH3), 3.27 (dd, 1H, J5a,5b 12.5 Hz and J5,4 7.0 Hz, H-5), 3.38 (s, 3H, OCH3), 3.45 (dd, 1H, J5a,5b 12.5 Hz and J5,4 7.0 Hz, H-50), 4.29 (t, 1H, J4,5 7.0 Hz, H-4), 4.60 (t, 2H, J2,3 6.5 Hz,H-2 and H-3), 5.00 (s, 1H, H-1). 13C NMR (CDCl3, 125.76 MHz): d 25.13(CH3), 26.61 (CH3), 53.98 (C-5), 55.45 (OCH3), 82.26 (C-3), 85.34 (C-2),85.60 (C-4), 110.04 (C-1), 112.91 (C-6).
80%	With sodium azide In N,N-dimethyl-formamide at 50℃; for 10h;
67%	With sodium azide In N,N-dimethyl-formamide for 2h; Heating;
	With sodium azide In N,N-dimethyl-formamide at 120℃;
	With sodium azide In N,N-dimethyl-formamide at 120℃;

Reference： [1]Ferreira, Sabrinab; Sodero, Ana C. R.; Cardoso, Mariana F. C.; Lima, Emerson S.; Kaiser, Carlos R.; Silva Jr., Floriano P.; Ferreira, Vitor F. [Journal of Medicinal Chemistry, 2010, vol. 53, # 6, p. 2364 - 2375]
[2]Burtsev, Ivan D.; Volov, Alexander N. [Journal of Organometallic Chemistry, 2020, vol. 922]
[3]Moreau, Christelle; Kirchberger, Tanja; Swarbrick, Joanna M.; Bartlett, Stephen J.; Fliegert, Ralf; Yorgan, Timur; Bauche, Andreas; Harneit, Angelika; Guse, Andreas H.; Potter, Barry V. L. [Journal of Medicinal Chemistry, 2013, vol. 56, # 24, p. 10079 - 10102]
[4]Saito, Seiki; Yokoyama, Hajime; Ishikawa, Teruhiko; Niwa, Nobuko; Morikawe, Toshio [Tetrahedron Letters, 1991, vol. 32, # 5, p. 663 - 666]
[5]Kumar, Dhananjay; Mishra, Kunj B.; Mishra, Bhuwan B.; Mondal, Saheli; Tiwari, Vinod K. [Steroids, 2014, vol. 80, p. 71 - 79]
[6]Evangelista, Tereza Cristina Santos; Aquino, Gabriel Alves Souto de; Donza, Marcio Roberto H.; Leitão, Rafael Lisboa; Carvalho, Victor Salarolli de; Kaiser, Carlos Roland; Ferreira, Sabrina Baptista [Journal of Carbohydrate Chemistry, 2021, vol. 40, # 5, p. 243 - 268]
[7]Bichard, Claire J. F.; Fairbanks, Antony J.; Fleet, George W. J.; Ramsden, Nigel G.; Vogt, Klaus; et al. [Tetrahedron Asymmetry, 1991, vol. 2, # 9, p. 901 - 912]
[8]Sarabia-Garcia, Francisco; Lopez-Herrera, F. Jorge [Tetrahedron, 1996, vol. 52, # 13, p. 4757 - 4768]
[9]Campos, Vinicius R.; Cunha, Anna C.; Silva, Wanderson A.; Ferreira, Vitor F.; Santos De Sousa, Carla; Fernandes, Patrícia D.; Moreira, Vinícius N.; Da Rocha, David R.; Dias, Flaviana R. F.; Montenegro, Raquel C.; De Souza, Maria C. B. V.; Boechat, Fernanda Da C. S.; Franco, Caroline F. J.; Resende, Jackson A. L. C. [RSC Advances, 2015, vol. 5, # 116, p. 96222 - 96229]
[10]Dias, Flaviana R.F.; Novais, Juliana S.; Devillart, Talita A. do Nascimento Santos; da Silva, Wanderson Amaral; Ferreira, Matheus O.; Loureiro, Raquel de S.; Campos, Vinícius R.; Ferreira, Vitor F.; de Souza, Maria C.B.V.; Castro, Helena C.; Cunha, Anna C. [European Journal of Medicinal Chemistry, 2018, vol. 156, p. 1 - 12]

7
[ 4137-56-8 ]
[ 23202-81-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside With sodium tetrahydroborate In dimethyl sulfoxide at 85℃; for 13h; Stage #2: With ammonium chloride In dimethyl sulfoxide	Methyl 2,3-0-isopropyliden-5-deoxy- β -D-ribofuranoside (7); A solution of compound 6 (5.12 g, 14.3 mmol) in DMSO (40 mL) was treated with NaBH4 (2.16 g, 57.1 mmol) and the mixture was stirred at 85°C for 13 hours. The reaction ended by adding a saturated solution of NH4Cl (200 mL). Then CH2Cl2 (200 mL) was added. The organic phase was washed with a saturated solution of sodium chloride (4 x 100 mL). It was dried (Na2SO4) and the solvent was evaporated. The residue was purified by column chromatography using CH2Cl2 as eluant to obtain the desired product 7 with a 100% yield.
96.7%	With sodium tetrahydroborate; N,N-dimethyl acetamide at 75 - 90℃;	3 Example 3: Preparation of a compound of formula 3 The compound of formula 2 (317 g) was sequentially added to the reaction flask.N,N-dimethylacetamide (915g),Potassium borohydride (57.1 g),Warm up to an internal temperature of 75 to 90 ° C,React at this temperature for 15 to 25 hours,After the LC monitors the reaction,Cool to room temperature and add water (2.3 kg) to quench the reaction.Add n-hexane (1.2kg) and extract three times.Combine the organic layers,Concentrated to dryness,A colorless liquid compound of formula 3, 161.0 g,The yield was 96.7%.
93.3%	With sodium tetrahydroborate; triethylamine In N,N-dimethyl acetamide at 85 - 90℃; for 10h; Inert atmosphere;	3 Example 1 Under nitrogen protection, 1-methoxy-2,3-O-isopropylidene-5-O-p-toluenesulfonyl-β-D-ribofuranoside (80.0 g, 0.22 mol) was sequentially added to the reaction flask. , N, N-dimethylacetamide 120ml, sodium borohydride (12.6g,0.33 mol), triethylamine (46 ml, 0.33 mol). Warming to 85-90°C,The reaction was incubated at this temperature for 10 hours and TLC monitored the reaction as complete.After cooling to room temperature, 10% hydrochloric acid (160 mL) was added dropwise in an ice-water bath. Extract with toluene (3*100 ml), combine the toluene phase, wash with water,Toluene was dried over anhydrous sodium sulfate and distilled under reduced pressure to give 39.2 g (yield: 93.3%) of a colorless transparent liquid with a GC content of 97.5%.

89%	With sodium tetrahydroborate In dimethyl sulfoxide at 20℃; for 2h;
83%	With lithium aluminium tetrahydride In diethyl ether; toluene Heating;
83%	With sodium tetrahydroborate In dimethyl sulfoxide at 80℃; for 4h;
71.8%	With sodium tetrahydroborate; acetic acid In dimethyl sulfoxide at 80 - 85℃; for 20h;	1 Methyl-2,3-O-isopropylidene-5-deoxy-β-D-ribofuranoside (3) 20g of sodium borohydride (NaBH4) was reacted with crude methyl-2,3-O-isopropylidene-5-O-tosyl-β-D-ribofuranoside (2) (50g, 140mmol) in 400ml of dimethyl sulfoxide solution for 20h at 80-85°C. After cooling the flask to room temperature, the reaction mixture was poured into 400ml of 1% aqueous acetic acid solution and stirred for 30min. The residue was extracted with chloroform and the collected organic layer was washed with sufficient amount of water. After dried with anhydrous magnesium sulfate, chloroform was removed under reduced pressure to give a crude compound with light yellow colour. The main biproduct of this reaction was methyl-2,3-O-isopropylidene-β-D-ribofuranoside (1) due to the hydrolysis of sulfonyl group. The crude compound was further purified and yielded 20.2g of methyl-2,3-O-isopropylidene-5-deoxyβ -D-ribofuranoside (3) (71.8%) as a clear colourless liquid upon distillation. 1H NMR (CDCl3): 1.27 and 1.48 (2s, each 3H, CMe2), δ 1.31 (d, 3H, J=1.5Hz, H-5), 3.33 (s, 3H, OMe), 4.35 (q, 1H, J=7.7Hz, H-4), 4.51 (d, 1H, J=5.4Hz, H-2), 4.64 (d, 1H, J=5.8Hz, H-3), 4.94 (s, 1H, H-1).
67%	With lithium aluminium tetrahydride In diethyl ether; benzene for 18h; Heating;
	Multi-step reaction with 2 steps 1: acetone; sodium iodide 2: platinum; aqueous methanol. NaOH-solution / Hydrogenation
	With sodium tetrahydroborate In dimethyl sulfoxide

Reference： [1]Current Patent Assignee: COLL FARMA S L; RICHMOND COM IND Y FINANCIE - EP2241556, 2010, A1 Location in patent: Page/Page column 8
[2]Current Patent Assignee: GUANG AN KINGDAY PHARMA CHEM - CN109369736, 2019, A Location in patent: Paragraph 0049; 0050; 0051
[3]Current Patent Assignee: SHANGHAI ACEBRIGHT PHARMACEUTICALS GROUP CO LTD - CN107365333, 2017, A Location in patent: Paragraph 0041-0048
[4]Sairam, Pothukuchi; Puranik, Ramachandra; Sreenivasa Rao, Bhatraju; Veerabhadra Swamy, Ponnapalli; Chandra, Sharad [Carbohydrate Research, 2003, vol. 338, # 4, p. 303 - 306]
[5]Wang, Guangyi; Tam, Robert C.; Gunic, Esmir; Du, Jinfa; Bard, Josie; Pai, Bharati [Journal of Medicinal Chemistry, 2000, vol. 43, # 13, p. 2566 - 2574]
[6]Ler, Geraldine J. M.; Xu, Weijun; Mak, Jeffrey Y. W.; Liu, Ligong; Bernhardt, Paul V.; Fairlie, David P. [Chemistry - A European Journal, 2019, vol. 25, # 68, p. 15594 - 15608]
[7]Current Patent Assignee: NANOMED HOLDINGS - EP2393472, 2019, B1 Location in patent: Paragraph 0142; 0147; 0148
[8]Snyder. Joseph R.; Serianni, Anthony S. [Carbohydrate Research, 1987, vol. 163, p. 169 - 188]
[9]Shunk et al. [Journal of the American Chemical Society, 1955, vol. 77, p. 2210]
[10]Mekala, Nagaraju; Moturu, Murthy V.R.K.; Dammalapati, Rao V.L.N.; Parimi, Atchuta R. [Organic Process Research and Development, 2016, vol. 20, # 3, p. 609 - 614]

8
[ 4137-56-8 ]
[ 38838-05-0 ]

Yield	Reaction Conditions	Operation in experiment
89%	With tetrabutylammomium bromide In N,N-dimethyl-formamide for 24h; Heating;

Reference： [1]Stick; Stubbs; Tilbrook [Australian Journal of Chemistry, 2001, vol. 54, # 3, p. 181 - 183]

9
[ 67-56-1 ]
D-Ribose [ No CAS ]
[ 98-59-9 ]
[ 67-64-1 ]
[ 4137-56-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: methanol; D-Ribose; acetone With hydrogenchloride for 3h; Reflux; Stage #2: p-toluenesulfonyl chloride With pyridine In dichloromethane at 20℃; for 24h;
40%	Stage #1: methanol; D-Ribose; acetone With hydrogenchloride Stage #2: p-toluenesulfonyl chloride With pyridine

Reference： [1]Lopes, João Paulo Bizarro; Silva, Luana; da Costa Franarin, Gabriela; Antonio Ceschi, Marco; Seibert Lüdtke, Diogo; Ferreira Dantas, Rafael; de Salles, Cristiane Martins Cardoso; Paes Silva-Jr, Floriano; Roberto Senger, Mario; Alvim Guedes, Isabella; Emmanuel Dardenne, Laurent [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 20, p. 5566 - 5577]
[2]Stick; Stubbs; Tilbrook [Australian Journal of Chemistry, 2001, vol. 54, # 3, p. 181 - 183]

10
[ 57412-08-5 ]
[ 4137-56-8 ]
methyl 2,3-O-isopropylidene-5-O-(5'-(para-phenylene)-10',15',20'-tri(p-tolyl)porphyrin)-β-D-ribofuranoside [ No CAS ]

Reference： [1]Polish Journal of Chemistry,2002,vol. 76,p. 543 - 550

11
[ 123-08-0 ]
[ 4137-56-8 ]
methyl 2,3-O-isopropylidene-5-O-(p-formylphenyl)-β-D-ribofuranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium hydride In N,N-dimethyl-formamide at 60℃; for 20h;

Reference： [1]Kus [Polish Journal of Chemistry, 2002, vol. 76, # 4, p. 543 - 550]

12
[ 4137-56-8 ]
[ 57412-06-3 ]
methyl 2,3-O-isopropylidene-5-O-(5'-(meta-phenylene)-10',15',20'-tri(p-tolyl)porphyrin)-β-D-ribofuranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With sodium hydride In N,N-dimethyl-formamide at 60 - 70℃; for 7h;

Reference： [1]Kus [Polish Journal of Chemistry, 2002, vol. 76, # 4, p. 543 - 550]

13
[ 4137-56-8 ]
[ 6328-58-1 ]
[ 676557-61-2 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 6-methyl-2-methylthiopyrimidin-4-one With sodium hydride In N,N-dimethyl-formamide at 80℃; for 1h; Stage #2: methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside In N,N-dimethyl-formamide at 80℃;

Reference： [1]Abdel-Rahman, Adel A.-H.; Abdel-Megied, Ahmed E.-S.; Goda, Adel E.-S.; Zeid, Ibrahim F.; El Ashry, El Sayed H. [Nucleosides, nucleotides and nucleic acids, 2003, vol. 22, # 11, p. 2027 - 2038]

14
[ 4137-56-8 ]
[ 5751-17-7 ]
[ 676557-62-3 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: 6-n-propyl-2-methylthio-4-pyrimidone With sodium hydride In N,N-dimethyl-formamide at 80℃; for 1h; Stage #2: methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside In N,N-dimethyl-formamide at 80℃;

Reference： [1]Abdel-Rahman, Adel A.-H.; Abdel-Megied, Ahmed E.-S.; Goda, Adel E.-S.; Zeid, Ibrahim F.; El Ashry, El Sayed H. [Nucleosides, nucleotides and nucleic acids, 2003, vol. 22, # 11, p. 2027 - 2038]

15
[ 4137-56-8 ]
[ 20651-30-3 ]
[ 676557-59-8 ]

Reference： [1]Nucleosides, nucleotides and nucleic acids,2003,vol. 22,p. 2027 - 2038

16
[ 4137-56-8 ]
[ 5751-20-2 ]
[ 676557-57-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: 2-methylthio-1H-pyrimidin-4-one With sodium hydride In N,N-dimethyl-formamide at 80℃; for 1h; Stage #2: methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside In N,N-dimethyl-formamide at 80℃;

Reference： [1]Abdel-Rahman, Adel A.-H.; Abdel-Megied, Ahmed E.-S.; Goda, Adel E.-S.; Zeid, Ibrahim F.; El Ashry, El Sayed H. [Nucleosides, nucleotides and nucleic acids, 2003, vol. 22, # 11, p. 2027 - 2038]

17
[ 4137-56-8 ]
[ 6991-65-7 ]

Yield	Reaction Conditions	Operation in experiment
67%	With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 1.5h;

Reference： [1]Ivanova; Valiullina; Shitikova; Miftakhov [Russian Journal of Organic Chemistry, 2007, vol. 43, # 5, p. 742 - 746]

18
[ 4137-56-8 ]
[ 14131-74-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside With sodium azide In N,N-dimethyl-formamide at 120℃; for 20h; Stage #2: With palladium on activated charcoal; hydrogen In ethanol for 3h;
	Multi-step reaction with 2 steps 1: 67 percent / NaN₃ / dimethylformamide / 2 h / Heating 2: 100 percent / Ph₃P / tetrahydrofuran / Ambient temperature
	Multi-step reaction with 2 steps 1: sodium azide / N,N-dimethyl-formamide / 16 h / 120 °C 2: triphenylphosphine / tetrahydrofuran / 16 h / 20 °C

	Multi-step reaction with 2 steps 1: sodium azide / N,N-dimethyl-formamide / 120 °C 2: palladium 10% on activated carbon; ethanol
	Multi-step reaction with 2 steps 1: sodium azide / N,N-dimethyl-formamide / 120 °C 2: palladium on activated charcoal; hydrogen / ethanol / 3040.2 Torr

Reference： [1]Dias, Flaviana R.F.; Guerra, Fabiana S.; Lima, Fernanda A.; de Castro, Yasmin K.C.; Ferreira, Vitor F.; Campos, Vinícius R.; Fernandes, Patrícia D.; Cunha, Anna C. [Journal of the Brazilian Chemical Society, 2021, vol. 32, # 3, p. 476 - 489]
[2]Sarabia-Garcia, Francisco; Lopez-Herrera, F. Jorge [Tetrahedron, 1996, vol. 52, # 13, p. 4757 - 4768]
[3]Moreau, Christelle; Kirchberger, Tanja; Swarbrick, Joanna M.; Bartlett, Stephen J.; Fliegert, Ralf; Yorgan, Timur; Bauche, Andreas; Harneit, Angelika; Guse, Andreas H.; Potter, Barry V. L. [Journal of Medicinal Chemistry, 2013, vol. 56, # 24, p. 10079 - 10102]
[4]Campos, Vinicius R.; Cunha, Anna C.; Silva, Wanderson A.; Ferreira, Vitor F.; Santos De Sousa, Carla; Fernandes, Patrícia D.; Moreira, Vinícius N.; Da Rocha, David R.; Dias, Flaviana R. F.; Montenegro, Raquel C.; De Souza, Maria C. B. V.; Boechat, Fernanda Da C. S.; Franco, Caroline F. J.; Resende, Jackson A. L. C. [RSC Advances, 2015, vol. 5, # 116, p. 96222 - 96229]
[5]Dias, Flaviana R.F.; Novais, Juliana S.; Devillart, Talita A. do Nascimento Santos; da Silva, Wanderson Amaral; Ferreira, Matheus O.; Loureiro, Raquel de S.; Campos, Vinícius R.; Ferreira, Vitor F.; de Souza, Maria C.B.V.; Castro, Helena C.; Cunha, Anna C. [European Journal of Medicinal Chemistry, 2018, vol. 156, p. 1 - 12]

19
[ 4137-56-8 ]
methyl 5-S-ethyl-2,3-O-isopropylidene-5-thio-β-D-ribofuranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86.5%	With ethanethiol In methanol; diethyl ether; sodium methylate	1.C Synthesis of ETR C. Methyl 5-deoxy-5-ethylthio-2,3-O-isopropylidene-β-D-ribofuranoside (III). A solution of ethanethiol (11.5 ml, 155 mmol) in 1N sodium methoxide in methanol (150 ml, 150 mmol sodium methoxide) was added to a solution of methyl 2,3-O-isopropylidene-5-O-p-toluenesulfonyl-β-D-ribofuranoside (50 g, 140 mmol in 200 ml dry methanol) and heated at reflux for 24 h. Solvents were removed by evaporation in vacuo, and the sticky residue was taken up in diethyl ether (300 ml) and washed with water (4*100 ml). The ether phase was dried and concentrated in vacuo to furnish a viscous oil. Fractional distillation (70° C. at 0.06 Torr) using a short-path distillation apparatus afforded 30.0 g (86.5% yield) of methyl 5-deoxy-5-ethylthio2,3-O-isopropylidene-β-D-ribofuranoside (III) as a colorless, viscous oil. TLC (silica; 25% ethylacetate in hexane):
	Multi-step reaction with 2 steps 1: 91 percent / dimethylformamide / 6 h / 120 - 130 °C 2: 57 percent / diethyl ether; tetrahydrofuran / 0.33 h / -40 °C

Reference： [1]Current Patent Assignee: EXELIXIS INC - US5366954, 1994, A
[2]Pakulski, Zbigniew; Pierozynski, Donat; Zamojski, Aleksander [Tetrahedron, 1994, vol. 50, # 9, p. 2975 - 2992]

20
[ 4137-56-8 ]
methyl 5-deoxy-5-fluoro-2,3-O-isopropylidene-β-D-ribofuranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With tetrabutyl ammonium fluoride In tetrahydrofuran; acetonitrile for 4h;
82%	With tetrabutyl ammonium fluoride In tetrahydrofuran; acetonitrile	18 Methyl 5-Deoxy-5-fluoro 2,3-O-(1-methylethylidene)-β-D-ribofuranoside Methyl 5-Deoxy-5-fluoro 2,3-O-(1-methylethylidene)-β-D-ribofuranoside Methyl 2,3-O-(1-methylethylidene)-5-O-(p-toluenesulfonyl)-β-ribofuranoside (28.7 g, 80 mmol) was dissolved in dry acetonitrile (100 ml). Tetra-n-butylammonium fluoride (100 ml, 1.0M in THF) was added dropwise and the reaction mixture was heated at 80° C. for 72 h. After cooling to room temperature, the mixture was diluted with dichloromethane (200 ml), washed with water (3*50 ml) and dried (MgSO4). Evaporation provided a residue which was purified by flash chromatography eluding with a mixture of ethyl acetate and n-heptane (1:3) to give methyl 5-deoxy-5-fluoro-2,3-O-(1-methylethylidene)-β-D-ribofuranoside (13.6 g, 82%) as a clear oil, 1 H NMR (CDCl3) δ1.34 (3H, s, CH3), 1.50 (3H, s, CH3), 3.35 (3H, s, --OCH3), 4.29-4.48 (3H, m, H-4, H-5a and H-5b), 4.60 (1H, d, H-3), 4.70 (1H, d, H-2), 4.99 (1H, d, H-1).
73%	With tetrabutyl ammonium fluoride In tetrahydrofuran; acetonitrile for 24h; Inert atmosphere; Reflux;

Reference： [1]Li, Xiang-Guo; Dall'Angelo, Sergio; Schweiger, Lutz F.; Zanda, Matteo; O'Hagan, David [Chemical Communications, 2012, vol. 48, # 43, p. 5247 - 5249]
[2]Current Patent Assignee: NOVO NORDISK A/S - US5589467, 1996, A
[3]Downey, A. Michael; Pohl, Radek; Roithová, Jana; Hocek, Michal [Chemistry - A European Journal, 2017, vol. 23, # 16, p. 3910 - 3917]

21
[ 124-41-4 ]
[ 130288-32-3 ]
[ 4137-56-8 ]
[ 901776-28-1 ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: sodium methylate; tert-butyl (2-oxotetrahydrothiophen-3-yl)carbamate In methanol for 0.166667h; Stage #2: methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside In methanol for 3h; Heating / reflux;	20.1 EXAMPLE 202-amino-4-(((2S,3S,4R,5R)-5-(6-(2-(dimethylamino)ethylamino)-9H-purin-9-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl)methylthio)butanoic acid 19aStep 1: methyl 2-(tert-butoxycarbonylamino)-4-(((3aS,4S,6R,6aR)-6-methoxy-2,2-dimethyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methylthio)butanoate 14A solution of N-tert-butoxycarbonyl-DL-homocysteine thiolactone 4 (9.1 g, 41.9 mmol) in NaOMe (0.5 M in methanol, 84 ml, 42 mmol) was stirred under a nitrogen atmosphere for 10 minutes. Methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside 13 (10.0 g, 27.9 mmol) was then added and the mixture was reflux for 3 hours. After the reaction had cooled to room temperature, the solvent was evaporated and the crude material was added to ethyl acetate (200 ml). The ethyl acetate solution was washed with saturated NaHCO3 (2×100 ml), 5% HCl (2×100 ml), and brine (100 ml). The ethyl acetate solution was then dried with MgSO4, filtered and evaporated to give the crude product. The title compound 14 was obtained in 83% yield (10.1 g) after purification by flash chromatography using 25% ethyl acetate and 75% hexanes. MS:calc 435.53; found 458 (M+Na+)

Reference： [1]Current Patent Assignee: MIRATI THERAPEUTICS, INC. - US2008/132525, 2008, A1 Location in patent: Page/Page column 20

22
[ 4137-56-8 ]
[ 75-33-2 ]
[ 158420-11-2 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium methylate In N,N-dimethyl-formamide at 90℃; for 5h;

Reference： [1]Location in patent: experimental part Pal, Tarun Kumar; Pathak, Tanmaya [Carbohydrate Research, 2008, vol. 343, # 16, p. 2826 - 2829]

23
[ 4137-56-8 ]
[ 100-53-8 ]
[ 158513-63-4 ]

Yield	Reaction Conditions	Operation in experiment
81%	With sodium methylate In N,N-dimethyl-formamide at 90℃; for 5h;

Reference： [1]Location in patent: scheme or table Pal, Tarun Kumar; Pathak, Tanmaya [Carbohydrate Research, 2008, vol. 343, # 16, p. 2826 - 2829]

24
[ 4137-56-8 ]
[ 50600-40-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium iodide; In butanone; at 80℃; for 17h;	A mixture of C (150 g), finely powdered sodium iodide (130 g) and butanone (1 .5 L) was stirred at 80 C for 17 hours. The resulting mixture was cooled to 20-25 C, washed 3 times with saturated aqueous sodium hydrogen carbonate (3 chi 300 mL) and concentrated under reduced pressure to yield D' (132 g, 100 %).
100%	With sodium iodide; In acetonitrile; for 12h;Reflux;	Compound 5 (10 g, 31.8 mmol) was dissolved in acetonitrile (104 ml)Sodium iodide (12.5 g) was added and the mixture was refluxed for 12 h.Cooling, filtering, evaporating the solvent, adding isopropyl ether, stirring, filtering,Isopropyl ether, and the filtrate was evaporated under reduced pressure to give a yellow oil 1 (8.5 g, 100%). No treatment, directly into the next reaction.
97%	With sodium iodide; In butanone; for 24h;Reflux;	4 to 5 : A mixture of compound 4 (4.40 g, 12.30 mmol), NaI (5.03 g, 33.53 mmol) in 2- butanone (50 mL) was refluxed for 24 h. The solvent was evaporated and the residue was diluted in Et2O. Filtration gave a solution, which was evaporated and dried under vacuum to give light yellow oil 5 (3.75 g, 97%)

48.8%

With sodium iodide; In butanone; at 120℃; for 24h;

A mixture of compound 13 (190.0 mg, 0.53 mmol, 1.0 eq), NaI (220 mg, 1.47 mmol, 2.8 eq) in 2-butanone (10 mL) was heated at reux for 24 h. The solvent was evaporated under vacuum to give a brown oil, which was purified by column chromatography on silica gel (PE: EtOAc =80:1) to give the title product as a pale yellow oil (48.8% yield). 1H NMR (300 MHz, CDCl3) delta 1.33 (s, 3 H), 1.45 (s, 3 H), 3.16~3.20 (t, 1 H), 3.27~3.34 (dd, 1 H), 3.35 (s, 3 H), 4.42~4.47 (dd, 1 H), 4.62~4.64 (d, 1 H), 4.76~4.78 (d, 1 H), 5.06 (s, 1 H).

Reference： [1]Patent: WO2013/92900,2013,A1 .Location in patent: Page/Page column 46
[2]Patent: CN102212095,2016,B .Location in patent: Paragraph 0041; 0042; 0043
[3]Journal of Organic Chemistry,2009,vol. 74,p. 2271 - 2277
[4]Patent: WO2010/85377,2010,A2 .Location in patent: Page/Page column 53
[5]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3598 - 3602

25
[ 4137-56-8 ]
[ 274693-55-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3598 - 3602
[2]Patent: EP2666771,2013,A1

26
[ 4137-56-8 ]
[ 274693-54-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3598 - 3602

27
[ 4137-56-8 ]
[ 274693-53-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3598 - 3602

28
(3aR,3a'R,5S,5'S,6R,6aR,6'R,6a'R)-5,5'-diselanediylbis(methylene)bis(2,2-dimethyltetrahydrofuro[2,3-d][1,3]-dioxol-6-ol) [ No CAS ]
[ 4137-56-8 ]
[ 1414863-59-4 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: (3aR,3a'R,5S,5'S,6R,6aR,6'R,6a'R)-5,5'-diselanediylbis(methylene)bis(2,2-dimethyltetrahydrofuro[2,3-d][1,3]-dioxol-6-ol) With sodium tetrahydroborate In tetrahydrofuran; ethanol at 20℃; for 0.166667h; Inert atmosphere; Stage #2: methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside In tetrahydrofuran; ethanol for 24h; Reflux; Inert atmosphere;	4.4. General procedure for the preparation of seleno disaccharides 7 General procedure: Under argon atmosphere, sodium borohydride (0.75 mmol) was added to a solution of the appropriate carbohydrate diselenide 4 (0.30 mmol) in THF (3 mL). Ethanol (2 mL) was then dropwise added and the clear solution formed was stirred at room temperature for 10 min. After this time a solution of the tosylate 3 (0.50 mmol in 2 mL THF) was slowly added. After stirring for 24 h under reflux, the reaction mixture was quenched with aqueous saturated NH4Cl (10 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were dried with MgSO4, filtered and concentrated. The crude product was purified by flash chromatography first eluting with hexanes and then with a mixture of hexanes/ethyl acetate (70:30).

Reference： [1]Affeldt, Ricardo F.; Baldassari, Lucas L.; Luedtke, Diogo S.; Braga, Hugo C. [Tetrahedron, 2012, vol. 68, # 51, p. 10470 - 10475,6]

29
[ 67816-34-6 ]
[ 4137-56-8 ]
[ 1414863-60-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: C₂₄H₃₈O₁₀Se₂ With sodium tetrahydroborate In tetrahydrofuran; ethanol at 20℃; for 0.166667h; Inert atmosphere; Stage #2: methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside In tetrahydrofuran; ethanol for 24h; Reflux; Inert atmosphere;	4.4. General procedure for the preparation of seleno disaccharides 7 General procedure: Under argon atmosphere, sodium borohydride (0.75 mmol) was added to a solution of the appropriate carbohydrate diselenide 4 (0.30 mmol) in THF (3 mL). Ethanol (2 mL) was then dropwise added and the clear solution formed was stirred at room temperature for 10 min. After this time a solution of the tosylate 3 (0.50 mmol in 2 mL THF) was slowly added. After stirring for 24 h under reflux, the reaction mixture was quenched with aqueous saturated NH4Cl (10 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were dried with MgSO4, filtered and concentrated. The crude product was purified by flash chromatography first eluting with hexanes and then with a mixture of hexanes/ethyl acetate (70:30).

Reference： [1]Affeldt, Ricardo F.; Baldassari, Lucas L.; Luedtke, Diogo S.; Braga, Hugo C. [Tetrahedron, 2012, vol. 68, # 51, p. 10470 - 10475,6]

30
[ 4137-56-8 ]
[ 50474-37-8 ]

Yield	Reaction Conditions	Operation in experiment
82%	With lithium diselenide In tetrahydrofuran; <i>tert</i>-butyl alcohol for 24h; Reflux; Inert atmosphere;	4.2. General procedure for the preparation of carbohydrate diselenides (4ac) General procedure: Under argon atmosphere lithium diselenide was generated by reaction of elemental selenium (95 mg, 1.2 mmol) with lithium triethylborohydride (1.2 mL, 1.2 mmol1 M solution in THF) at room temperature. The suspension was stirred for 20 min. After this time t-BuOH (0.2 mL) and THF (4 mL) were added at room temperature, followed by dropwise addition of a solution of the respective tosylate (0.5 mmol in 1 mL THF). After stirring for 24 h under reflux, the reaction mixture was quenched with aqueous saturated NH4Cl (10 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were dried with MgSO4, filtered and concentrated. The crude product was purified by flash chromatography eluting with a mixture of hexanes/ethyl acetate (80:20).

Reference： [1]Affeldt, Ricardo F.; Baldassari, Lucas L.; Luedtke, Diogo S.; Braga, Hugo C. [Tetrahedron, 2012, vol. 68, # 51, p. 10470 - 10475,6]

31
[ 41411-59-0 ]
[ 4137-56-8 ]
[3-((3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl)-3H-[1,2,3]triazol-4-yl]-methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With sodium azide In N,N-dimethyl-formamide at 100℃; for 10h; regioselective reaction;

Reference： [1]Dey, Santu; Pathak, Tanmaya [RSC Advances, 2014, vol. 4, # 18, p. 9275 - 9278]

32
[ 1854-83-7 ]
[ 4137-56-8 ]
[ 1028182-98-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium azide In N,N-dimethyl-formamide at 100℃; for 5h; regioselective reaction;

Reference： [1]Dey, Santu; Pathak, Tanmaya [RSC Advances, 2014, vol. 4, # 18, p. 9275 - 9278]

33
[ 4137-56-8 ]
[ 630108-94-0 ]
N-tert-butoxycarbonyl-S-(5-deoxy-1-O-methyl-2,3-O-isopropylidene-β-D-ribofuranos-5-yl)-L-homocysteine tert-butyl ester [ No CAS ]
[ 601491-40-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-tert-butoxycarbonyl-L-homocysteine tert-butyl ester With potassium hexamethylsilazane In tetrahydrofuran at 0 - 20℃; for 0.5h; Inert atmosphere; Stage #2: methyl 2,3-O-isopropylidene-5-O-p-tolylsulfonyl-β-D-ribofuranoside In tetrahydrofuran at 0 - 20℃; for 6h; Inert atmosphere;	General procedure for S_N2 reactions of homocysteine thiols with ribose electrophiles, analytical scale (0.1-0.15 mmol) General procedure: Base was added dropwise to an approximately 100 mM solution of thiol in THF at 0 °C. The reaction mixture was then moved to ambient temperature and stirred for 30 min. The reaction mixture was returned to 0 °C, at which time an approximately 1 M solution of electrophile in THF was added dropwise by syringe. The reaction mixture was moved to ambient temperature with stirring and monitored by TLC (1:3 EtOAc/hexanes). Upon consumption of starting material, the reaction mixture was quenched with saturated aqueous NH4Cl (10× volume), then extracted with four equal volumes of CH2Cl2. The combined organic layers were washed with five portions of water, then one portion of brine. The washed organic layer was dried over anhydrous MgSO4, filtered, and concentrated via rotary evaporation. 1H NMR spectrum of the crude product was obtained at 500 MHz in CDCl3, with the relative concentrations of key compounds determined by integration.

Reference： [1]Bolitho, Megan E.; Corcoran, Brendan J.; Showell-Rouse, Emily I.; Wang, Keeshia Q. [Carbohydrate Research, 2014, vol. 394, p. 32 - 38]

34
[ 14003-34-0 ]
[ 4137-56-8 ]
[ 1583293-61-1 ]
[ 1583293-67-7 ]