Gadthula Srinivas, Chu Chung K, Schinazi Raymond F
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602, USA.
Nucleosides Nucleotides Nucleic Acids. 2005;24(10-12):1707-27. doi: 10.1080/15257770500267170.
Since the discovery of 3'-azido-3'-deoxythymidine (AZT) and 2',3'-didehydro-2',3'-dideoxythymidine (d4T) as potent and selective inhibitors of the replication of human immunodeficiency virus (HIV), there has been a growing interest for the synthesis of 2',3'-didehydro-2',3'dideoxynucleosides with electron withdrawing groups on the sugar moiety. Here we described an efficient method for the synthesis of such nucleoside analogs bearing structural features of both AZT and d4T The key intermediate, 3-azido-1,2-bis-O-acetyl-5-O-benzoyl-3-deoxy-D-ribofuranose, 5 was synthesized from commercially available D-xylose in five steps, from which a series of pyrimidine and purine nucleosides were synthesized in high yields. The resultant protected nucleosides were converted to target nucleosides using appropriate chemical modifications. The final nucleosides were evaluated as potential anti-HIV agents.
自从发现3'-叠氮基-3'-脱氧胸苷（AZT）和2'，3'-二脱氢-2'，3'-二脱氧胸苷（d4T）作为人类免疫缺陷病毒（HIV）复制的有效且选择性抑制剂以来，人们对在糖部分带有吸电子基团的2'，3'-二脱氢-2'，3'-二脱氧核苷的合成越来越感兴趣。在此，我们描述了一种有效合成此类具有AZT和d4T结构特征的核苷类似物的方法。关键中间体3-叠氮基-1,2-双-O-乙酰基-5-O-苯甲酰基-3-脱氧-D-核糖呋喃糖（5）由市售的D-木糖经五步合成，由此以高产率合成了一系列嘧啶和嘌呤核苷。使用适当的化学修饰将所得的保护核苷转化为目标核苷。对最终的核苷作为潜在抗HIV药物进行了评估。
