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【结 构 式】 
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【分子编号】17701 【品名】[(2R,3R,4S,5R)-4-fluoro-3-hydroxy-5-methoxytetrahydro-2-furanyl]methyl benzoate 【CA登记号】 |
【 分 子 式 】C13H15FO5 【 分 子 量 】270.2575032 【元素组成】C 57.78% H 5.59% F 7.03% O 29.6% |
合成路线1
该中间体在本合成路线中的序号：(XIV)The reaction of 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranose (XI) with HBr in acetic acid gives the bromosugar (XII), which is methylated with methanol/K2CO3 in THF, yielding the 1-O-methyl glucoside (XIII). The selective benzoylation of (XIII) with benzoyl chloride in pyridine at -30 C affords the 5-O-benzoyl glucoside (XIV), which is treated with CS2/methyl iodide and NaH in DMF, giving compound (XV). The reduction of (XV) with tributyltin hydride and AIBN in refluxing toluene yields the 3-deoxy glucoside (XVI), which is condensed with 6-chloropurine (V) in refluxing hexamethyldisylazane, affording 9-(5-O-benzoyl-2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (XVII). Finally, this compound is debenzoylated with methanolic ammonia at 100 C in a sealed tube.
| 【1】 Siddiqui, M.A.; Marquez, V.E.; Driscoll, J.S.; Barchi, J.J. Jr.; Wysocki, R.J. Jr.; A more expedient approach to the synthesis of anti-HIV-active 2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl nucleosides. Synthesis 1991, 11, 11, 1005-8. |
| 【2】 Castaner, J.; Graul, A.; Silvestre, J.S.; Lodenosine. Drugs Fut 1998, 23, 11, 1176-1189. |
| 【3】 Driscoll, J.S.; Roth, J.S.; Broder, S.; Kelley, J.A.; Tseng, C.K.-H.; Mitsuya, H.; Marquez, V.E.; 2',3'-Dideoxy-2'-fluoro-ara-A, an acid-stable purine nucleoside active against human immunodeficiency virus (HIV). Biochem Pharmacol 1987, 36, 17, 2719-22. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 17692 | 6-Chloropurine; 6-chloro-9H-purine | 87-42-3 | C5H3ClN4 | 详情 | 详情 |
| (XI) | 17698 | [(2R,3R,4S,5R)-3,5-bis(benzoyloxy)-4-fluorotetrahydro-2-furanyl]methyl benzoate | C26H21FO7 | 详情 | 详情 | |
| (XII) | 17699 | (2R,3R,4S)-5-bromo-4-fluoro-2-(hydroxymethyl)tetrahydro-3-furanol | C5H8BrFO3 | 详情 | 详情 | |
| (XIII) | 17700 | (2R,3R,4S,5R)-4-fluoro-2-(hydroxymethyl)-5-methoxytetrahydro-3-furanol | C6H11FO4 | 详情 | 详情 | |
| (XIV) | 17701 | [(2R,3R,4S,5R)-4-fluoro-3-hydroxy-5-methoxytetrahydro-2-furanyl]methyl benzoate | C13H15FO5 | 详情 | 详情 | |
| (XV) | 17702 | ((2R,3R,4S,5R)-4-fluoro-5-methoxy-3-[[(methylsulfanyl)carbothioyl]oxy]tetrahydro-2-furanyl)methyl benzoate | C15H17FO5S2 | 详情 | 详情 | |
| (XVI) | 17703 | [(2S,4S,5R)-4-fluoro-5-methoxytetrahydro-2-furanyl]methyl benzoate | C13H15FO4 | 详情 | 详情 | |
| (XVII) | 17704 | [(2S,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methyl benzoate | C17H14ClFN4O3 | 详情 | 详情 |