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【结 构 式】 
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【分子编号】56924 【品名】(3R,5R)-5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-3-[(2,4,6-triisopropylphenyl)sulfanyl]dihydro-2(3H)-furanone 【CA登记号】 |
【 分 子 式 】C36H48O3SSi 【 分 子 量 】588.92682 【元素组成】C 73.42% H 8.22% O 8.15% S 5.44% Si 4.77% |
合成路线1
该中间体在本合成路线中的序号：(XXXIII)Condensation of the chiral lactone (IV) with 2,4,6-tris-isopropylphenylsulfanyl chloride (XXXII) by means of LiHMDS and TMS-OTf in THF gives the adduct (XXXIII), which is reduced with DIBAL in toluene to yield the lactol (XXXIV). Reaction of compound (XXXIV) with Ac2O and pyridine in THF affords the acetoxy derivative (XXXV), which is condensed with the silylated 5-fluorouracil (XXIII) by means of SnCl4 in dichloromethane to provide the nucleoside (XXXVI). Oxidation of the sulfanyl group of (XXXVI) with magnesium monoperoxyphthalate (MMPP) in THF, followed by desulfurization by heating with DBU in refluxing toluene, gives 5'-O-TBDPS-2',3'-dideoxy-2',3'-didehydro-5-fluoro-b-L-uridine (XXXVII), which by treatment with Bu4NF in THF yields 2',3'-dideoxy-2',3'-didehydro-b-L-uridine (XXXIX). Finally, this compound is converted into 2',3'-dideoxy-2',3'-didehydro-b-L-cytidine by conventional methods.
| 【1】 Bayes, M.; Sorbera, L.A.; Castaner, J.; ACH-126443. Drugs Fut 2002, 27, 12, 1131. |
| 【2】 Schinazi, R.F.; Liotta, D.C. (Emory University); [5-Carboxamido or 5-fluoro]-[2',3'-unsaturated or 3'-modified]-pyrimidine nucleosides. EP 0805683; JP 1998512887; US 5703058; WO 9622778 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 56922 | (5R)-5-({[tert-butyl(diphenyl)silyl]oxy}methyl)dihydro-2(3H)-furanone | C21H26O3Si | 详情 | 详情 | |
| (XXIII) | 47859 | 5-fluoro-2-[(trimethylsilyl)oxy]-4-pyrimidinyl trimethylsilyl ether; 5-fluoro-2,4-bis[(trimethylsilyl)oxy]pyrimidine | 17242-85-2 | C10H19FN2O2Si2 | 详情 | 详情 |
| (XXXII) | 56923 | 2,4,6-triisopropylbenzenesulfenyl chloride | C15H23ClS | 详情 | 详情 | |
| (XXXIII) | 56924 | (3R,5R)-5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-3-[(2,4,6-triisopropylphenyl)sulfanyl]dihydro-2(3H)-furanone | C36H48O3SSi | 详情 | 详情 | |
| (XXXIV) | 56925 | (3R,5R)-5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-3-[(2,4,6-triisopropylphenyl)sulfanyl]tetrahydro-2-furanol | C36H50O3SSi | 详情 | 详情 | |
| (XXXV) | 56926 | (3R,5R)-5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-3-[(2,4,6-triisopropylphenyl)sulfanyl]tetrahydro-2-furanyl acetate | C38H52O4SSi | 详情 | 详情 | |
| (XXXVI) | 56927 | 1-{(2S,3R,5R)-5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-3-[(2,4,6-triisopropylphenyl)sulfanyl]tetrahydro-2-furanyl}-5-fluoro-2,4(1H,3H)-pyrimidinedione | C40H51FN2O4SSi | 详情 | 详情 | |
| (XXXVII) | 56928 | 1-[(2S,5R)-5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2,5-dihydro-2-furanyl]-5-fluoro-2,4(1H,3H)-pyrimidinedione | C25H27FN2O4Si | 详情 | 详情 | |
| (XXXIX) | 56929 | 5-fluoro-1-[(2S,5R)-5-(hydroxymethyl)-2,5-dihydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione | C9H9FN2O4 | 详情 | 详情 |