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【结 构 式】 
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【分子编号】12801 【品名】9-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-9H-purin-6-ol 【CA登记号】890-38-0 |
【 分 子 式 】C10H12N4O4 【 分 子 量 】252.22984 【元素组成】C 47.62% H 4.8% N 22.21% O 25.37% |
合成路线1
该中间体在本合成路线中的序号：(I)5) The benzoylation of 2'-deoxyinosine (I) with benzoyl chloride in pyridine gives the 5'-O-benzoyl derivative (II), which is treated with 1,1'-thiocarbonyldiimidazole (DTI) in DMF to afford the 2'-O-thiocarbonyl derivative (III). The reaction of (III) with bis(tributyltin)oxide, polymethylhydroxysilane and AIBN in refluxing dioxane yields 5'-O-benzoyl-2',3'-dideoxyinosine (IV), which is finally deprotected with anhydrous NH3 in methanol. Another microbial conversion of 2',3'-dideoxyuridine to 2',3'-dideoxyinosine by transdideoxyribosylation with hypoxanthine in a culture medium of Escherichia coli ATCC 10798 is described, and industrially applicable methods for the purification of enzymatically or microbially obtained dideoxyinosines are reported.
| 【1】 Tanabe, T.; Otani, M.; Arai, M.; Yukawa, T. (Ajinomoto Co., Inc.); Method for the purification of dideoxyinosine. JP 1989175991 . |
| 【2】 Tanabe, T.; Otani, M.; Yukawa, T. (Ajinomoto Co., Inc.); Method for the purification of dideoxyinosine. JP 1989165390 . |
| 【3】 Prous, J.; Castaner, J.; DIDEOXYINOSINE. Drugs Fut 1990, 15, 6, 569. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 12801 | 9-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-9H-purin-6-ol | 890-38-0 | C10H12N4O4 | 详情 | 详情 |
| (II) | 12802 | [(2R,3S,5R)-3-hydroxy-5-(6-hydroxy-9H-purin-9-yl)tetrahydro-2-furanyl]methyl benzoate | C17H16N4O5 | 详情 | 详情 | |
| (III) | 12803 | [(2R,3S,5R)-5-(6-hydroxy-9H-purin-9-yl)-3-[(1H-imidazol-1-ylcarbothioyl)oxy]tetrahydro-2-furanyl]methyl benzoate | C21H18N6O5S | 详情 | 详情 | |
| (IV) | 12804 | [(2S,5R)-5-(6-hydroxy-9H-purin-9-yl)tetrahydro-2-furanyl]methyl benzoate | C17H16N4O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)A new synthesis of didanosine has been described: Treatment of 2'-deoxyadenosine (I) with adenosine deaminase (ADA) in water gives 2'-deoxyinosine (II), which is treated with vinyl acetate (III) and Candida antarctica lipase (CAL) in hot pyridine yielding 5'-O-acetyl-2'-deoxyinosine (IV). The reaction of (IV) with phenyl chlorothionoformate (V) and DMAP in acetonitrile affords the corresponding thiocarbonate (VI), which is treated with tributylstannane and AIBN in hot toluene to provide 5'-O-acetyl-2',3'-dideoxyinosine (VII). Finally, this compound is deacetylated with NH3 in methanol.
| 【1】 Santaniello, E.; Ciuffreda, P.; Casati, S.; Lipase-catalyzed protection of the hydroxy groups of the nucleosides inosine and 2'-deoxyinosine: A new chemoenzymatic synthesis of the antiviral drug 2',3'-dideoxyinosine. Bioorg Med Chem Lett 1999, 9, 11, 1577. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 18061 | (2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydro-3-furanol | 958-09-8 | C10H13N5O3 | 详情 | 详情 |
| (II) | 12801 | 9-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-9H-purin-6-ol | 890-38-0 | C10H12N4O4 | 详情 | 详情 |
| (III) | 24543 | vinyl acetate | 108-05-4 | C4H6O2 | 详情 | 详情 |
| (IV) | 37609 | [(2R,3S,5R)-3-hydroxy-5-(6-hydroxy-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate | C12H14N4O5 | 详情 | 详情 | |
| (V) | 25805 | 1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate | 1005-56-7 | C7H5ClOS | 详情 | 详情 |
| (VI) | 37610 | [(2R,3S,5R)-5-(6-hydroxy-9H-purin-9-yl)-3-[(phenoxycarbothioyl)oxy]tetrahydro-2-furanyl]methyl acetate | C19H18N4O6S | 详情 | 详情 | |
| (VII) | 37611 | [(2S,5R)-5-(6-hydroxy-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate | C12H14N4O4 | 详情 | 详情 |