1-甲基-5-(3-叠氮基-2,3-二脱氧-β-D-赤藓戊呋喃糖基)尿嘧啶和1-甲基-5-(3-叠氮基-2,3-二脱氧-2-氟-β-D-阿拉伯呋喃糖基)尿嘧啶的合成。3'-叠氮基-3'-脱氧胸苷的C-核苷类似物及其2'-“上”-氟类似物。
Synthesis of 1-methyl-5-(3-azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)uracil and 1-methyl-5-(3-azido-2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)uracil. The C-nucleoside isostere of 3'-azido-3'-deoxythymidine and its 2'-"up"-fluoro analogue.
作者信息
Sochacka E, Nawrot B, Pankiewicz K W, Watanabe K A
机构信息
Sloan-Kettering Institute for Cancer Research, Cornell University, New York, New York 10021.
出版信息
J Med Chem. 1990 Jul;33(7):1995-9. doi: 10.1021/jm00169a030.
1-Methyl-5-(3-azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)uracil (C-AZT), a C-nucleoside isostere of the potent anti-AIDS nucleoside 3'-azido-3'-deoxythymidine (AZT), was synthesized. 1-Methyl-2'-deoxy-5'-O-tritylpseudouridine (2a) was oxidized with CrO3/pyridine/Ac2O complex to 1-methyl-5-(5-O-trityl-beta-D-glycero-pentofuranos-3-ulosyl) uracil (12a), which was selectively reduced to 1-methyl-5-(5-O-trityl-beta-D-threo-pentofuranosyl)uracil (13a). Mesylation of 13a to 14a followed by nucleophilic displacement of the mesyloxy group with azide afforded 3'-azido-2',3'-dideoxy-5'-O-trityl-1-methylpseudoridine (15a), which was detritylated to C-AZT. In a similar manner, 1-methyl-5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil (C-FMAU, a potent antiherpetic nucleoside) was converted into the 3'-azido analogue (3'-azido-C-FMAU). Both C-AZT and 3'-azido-C-FMAU, however, did not exhibit any significant inhibitory activity against HIV in H9 cells.
1-甲基-5-(3-叠氮基-2,3-二脱氧-β-D-赤藓戊呋喃糖基)尿嘧啶（C-AZT），一种强效抗艾滋病核苷3'-叠氮基-3'-脱氧胸苷（AZT）的C-核苷类似物，被合成出来。1-甲基-2'-脱氧-5'-O-三苯甲基假尿苷（2a）用CrO3/吡啶/乙酸酐复合物氧化为1-甲基-5-(5-O-三苯甲基-β-D-甘油戊呋喃糖-3-酮糖基)尿嘧啶（12a），后者被选择性还原为1-甲基-5-(5-O-三苯甲基-β-D-苏式戊呋喃糖基)尿嘧啶（13a）。13a经甲磺酰化得到14a，随后用叠氮化物亲核取代甲磺酰氧基得到3'-叠氮基-2',3'-二脱氧-5'-O-三苯甲基-1-甲基假尿苷（15a），其脱三苯甲基后得到C-AZT。以类似方式，1-甲基-5-(2-脱氧-2-氟-β-D-阿拉伯呋喃糖基)尿嘧啶（C-FMAU，一种强效抗疱疹核苷）被转化为3'-叠氮基类似物（3'-叠氮基-C-FMAU）。然而，C-AZT和3'-叠氮基-C-FMAU在H9细胞中对HIV均未表现出任何显著的抑制活性。
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