Stereocontrolled synthesis of heterocyclic C-nucleosides. Protecting group effect and molecular modeling studies

J Org Chem. 2002 May 31;67(11):3724-32. doi: 10.1021/jo016345x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetals / chemistry
  • Borohydrides / chemistry
  • Cyclization
  • Imidazoles / chemical synthesis*
  • Indoles / chemical synthesis*
  • Models, Molecular
  • Nucleosides / chemical synthesis*
  • Oxidation-Reduction
  • Stereoisomerism

Substances

  • Acetals
  • Borohydrides
  • Imidazoles
  • Indoles
  • Nucleosides