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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Stereocontrolled synthesis of heterocyclic C-nucleosides. Protecting group effect and molecular modeling studies
Dominique Guianvarc'h1, Jean-Louis Fourrey, Marie-Elise Tran Huu Dau
1Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-Sur-Yvette, France.
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.
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