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【结 构 式】

【分子编号】55534

【品名】(1R,2S,3R,5R)-3-(6-amino-9H-purin-9-yl)-5-(hydroxymethyl)-1,2-cyclopentanediol

【CA登记号】

【 分 子 式 】C11H15N5O3

【 分 子 量 】265.272

【元素组成】C 49.81% H 5.7% N 26.4% O 18.09%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(I)

The selective silylation of (-)-aristeromycin (I) with Hdms-Cl and imidazole gives the monosilyl ether (II), which is treated with thiocarbonyl dimidazole (TCDI) in hot ethyl acetate to yield the cyclic thiocarbonate (III). The reaction of (III) with 1,3-dimethyl-1,3,2-diazaphospholidine (DMPDP) in refluxing THF affords the desired cyclopentene derivative (IV). In an alternative method, the reaction of (II) with methyl orthoformate provides the cyclic orthoester (V), which undergoes thermal elimination with acetic acid at high temperature giving the desired cyclopentene derivative (IV). The oxidation of (IV) with MCPBA in chloroform yields the N-oxide (VI), which by reaction with Br-CN in methanol affords the oxadiazole derivative (VII). The cleavage of the oxadiazole ring of (VII) and simultaneous methylation with TEA and Me-I provided the cyanoimino derivative (VIII), which is submitted to a Dimroth rearrangement by means of 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) in refluxing aqueous ethanol to give the methoxylated diaminopurine (IX). The reductive cleavage of the methoxyamino group of (IX) with Al/Hg in aqueous THF yields the silylated diaminopurine (X), which is deprotected with HCl in ethanol to afford the free diaminopurine precursor (XI). Finally, this compound is enzymatically deaminated by means of adenosine deaminase to furnish the target (-)-carbovir.

1 Exall, A.M.; et al.; Synthesis from (-)-aristeromycin and x-ray structure of (-)-carbovir. J Chem Soc - Perkins Trans I 1991, 10, 2467.
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) 55534 (1R,2S,3R,5R)-3-(6-amino-9H-purin-9-yl)-5-(hydroxymethyl)-1,2-cyclopentanediol C11H15N5O3 详情 详情
(II) 55535 (1R,2S,3R,5R)-3-(6-amino-9H-purin-9-yl)-5-({[hexyl(dimethyl)silyl]oxy}methyl)-1,2-cyclopentanediol C19H33N5O3Si 详情 详情
(III) 55536 (4R,6R)-4-(6-amino-9H-purin-9-yl)-6-({[hexyl(dimethyl)silyl]oxy}methyl)tetrahydro-3aH-cyclopenta[d][1,3]dioxole-2-thione C20H31N5O3SSi 详情 详情
(IV) 55537 9-[(1R,4S)-4-({[hexyl(dimethyl)silyl]oxy}methyl)-2-cyclopenten-1-yl]-9H-purin-6-amine; 9-[(1R,4S)-4-({[hexyl(dimethyl)silyl]oxy}methyl)-2-cyclopenten-1-yl]-9H-purin-6-ylamine C19H31N5OSi 详情 详情
(V) 55538 9-[(4R,6R)-6-({[hexyl(dimethyl)silyl]oxy}methyl)-2-methoxytetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-9H-purin-6-amine; 9-[(4R,6R)-6-({[hexyl(dimethyl)silyl]oxy}methyl)-2-methoxytetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-9H-purin-6-ylamine C21H35N5O4Si 详情 详情
(VI) 55539 6-amino-9-[(1R,4S)-4-({[hexyl(dimethyl)silyl]oxy}methyl)-2-cyclopenten-1-yl]-9H-purin-1-ium-1-olate C19H31N5O2Si 详情 详情
(VII) 55540 7-[(1R,4S)-4-({[hexyl(dimethyl)silyl]oxy}methyl)-2-cyclopenten-1-yl][1,2,4]oxadiazolo[3,2-i]purin-2(7H)-imine C20H30N6O2Si 详情 详情
(VIII) 55541 9-[(1R,4S)-4-({[hexyl(dimethyl)silyl]oxy}methyl)-2-cyclopenten-1-yl]-1-methoxy-1,9-dihydro-6H-purin-6-ylidenecyanamide C21H32N6O2Si 详情 详情
(IX) 55542 9-[(1R,4S)-4-({[hexyl(dimethyl)silyl]oxy}methyl)-2-cyclopenten-1-yl]-6-(methoxyamino)-9H-purin-2-ylamine; 9-[(1R,4S)-4-({[hexyl(dimethyl)silyl]oxy}methyl)-2-cyclopenten-1-yl]-6-(methoxyamino)-9H-purin-2-amine C20H34N6O2Si 详情 详情
(X) 55543 2-amino-9-[(1R,4S)-4-({[hexyl(dimethyl)silyl]oxy}methyl)-2-cyclopenten-1-yl]-9H-purin-6-ylamine; 9-[(1R,4S)-4-({[hexyl(dimethyl)silyl]oxy}methyl)-2-cyclopenten-1-yl]-9H-purine-2,6-diamine C19H32N6OSi 详情 详情
(XI) 55533 [(1S,4R)-4-(2,6-diamino-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol C11H14N6O 详情 详情
Extended Information