Stereoselective synthesis of 2',3'-dideoxynucleosides by addition of selenium electrophiles to glycals. A formal synthesis of D4T from 2-deoxyribose
Stereoselective synthesis of 2',3'-dideoxynucleosides by addition of selenium electrophiles to glycals. A formal synthesis of D4T from 2-deoxyribose
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DOI：
10.1021/jo9616825
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发表时间：
1997-03-07
影响因子：
3.6
通讯作者：
Castillon, S
中科院分区：
文献类型：
--
作者：
Diaz, Y;ElLaghdach, A;Castillon, S
2′, 3′-Dideoxynucleosides are among the most active agents against human immunodeficiency virus (HIV), which is the causative agent for acquired immunodeficiency syndrome (AIDS). In particular, 3′-azido-3′-deoxythymidine (AZT), 1 2′, 3′-dideoxyinosine (ddI), 1 2′, 3′-didehydro-2′-deoxythymidine (D4T), 2ab and 2′, 3′-dideoxycitidine (ddC) 2c, d have been approved for the treatment of AIDS.These compounds have been prepared by structural modification of naturally occurring nucleosides or through glycosylation reactions. 3 The main synthetic problem in this latter approach is the control of the stereoselectivity in the absence of substituents at position 2. 4 To overcome this drawback, several reports have described the use of easily removable groups, such as phenylsulfenyl or phenylselenenyl, at position 2 in the furanose ring, which efficiently control the stereoselectivity and enable 2′, 3′-dideoxy-and 2′, 3′-didehydro-2′, 3′-dideoxy nucleosides to be easily obtained. The preparation of the 2′, 3′-dideoxy-2′-phenylsulfenyl5 or 2′, 3′-dideoxy-2′-phenylselenenyl6 nucleosides usually involves four steps, and although good stereoselectivity is obtained in the glycosylation reaction, the validity of the method is limited by the low stereoselectivity in the sulfur or selenium introduction step (Scheme 1, via a).
