Guianvarc'h Dominique, Fourrey Jean-Louis, Tran Huu Dau Marie-Elise, Guérineau Vincent, Benhida Rachid
Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-Sur-Yvette, France.
J Org Chem. 2002 May 31;67(11):3724-32. doi: 10.1021/jo016345x.
We report herein a short stereocontrolled synthesis of heterocyclic C-nucleosides (indole, imidazole, benzimidazole, and 6-iodobenzimidazole). First, condensation of 2-lithiated heterocycles 2-5 with 5-(tert-butyldiphenylsilyl)-2,3-O-isopropylidene-D-gamma-ribonolactone (1) afforded the hemiacetals 6-9 in good yields. Then, borohydride reduction (NaBH(4)) of the protected hemiacetals proceeded stereoselectively to give predominantly the S diols 10-13, which upon Mitsunobu cyclization afforded the alpha-C-nucleosides 14-17. In contrast, the same PPh(3)/DEAD treatment of the 1:1 diastereomeric mixture of the free heterocyclic diols 10d and 11d gave exclusively the beta-anomers 14dbeta and 15dbeta, respectively, by a stereocontrolled process. The mechanisms of these stereocontrolled steps are discussed with the support of molecular modeling studies.
我们在此报告一种杂环C-核苷（吲哚、咪唑、苯并咪唑和6-碘苯并咪唑）的短程立体控制合成方法。首先，2-锂化杂环化合物2-5与5-(叔丁基二苯基硅基)-2,3-O-异亚丙基-D-γ-核糖内酯（1）缩合，以良好的产率得到半缩醛6-9。然后，对受保护的半缩醛进行硼氢化物还原（NaBH₄），立体选择性地主要生成S-二醇10-13，经 Mitsunobu 环化反应得到α-C-核苷14-17。相比之下，对游离杂环二醇10d和11d的1:1非对映体混合物进行相同的三苯基膦/偶氮二甲酸二乙酯处理，通过立体控制过程分别仅得到β-端基异构体14dβ和15dβ。在分子建模研究的支持下，讨论了这些立体控制步骤的机制。
