title: Stereocontrolled synthesis of heterocyclic C-nucleosides. Protecting group effect and molecular modeling studies.
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.
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-Sur-Yvette, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Guianvarc'h
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Fourrey
authors.forename: Marie-Elise
authors.initials: ME
authors.lastname: Tran Huu Dau
authors.forename: Vincent
authors.initials: V
authors.lastname: Guérineau
authors.forename: Rachid
authors.initials: R
authors.lastname: Benhida
mesh_terms: D000080:Acetals / Q000737:chemistry; D001894:Borohydrides / Q000737:chemistry; D003500:Cyclization; D007093:Imidazoles / Q000138:chemical synthesis*; D007211:Indoles / Q000138:chemical synthesis*; D008958:Models, Molecular; D009705:Nucleosides / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D000080:Acetals; D001894:Borohydrides; D007093:Imidazoles; D007211:Indoles; D009705:Nucleosides