Direct synthesis of pyrrole nucleosides by the stereospecific sodium salt glycosylation procedure

Abstract

Abstract A stereospecific high‐yield glycosylation of preformed fully aromatic pyrroles has been accomplished for the first time. Reaction of the sodium salt of pyrrole‐2‐carbonitrile ( 1a ) and pyrrole‐2,4‐dicarbonitrile ( 1b ) with 1‐chloro‐2‐deoxy‐3,5‐di‐ O ‐ p ‐toluoyl‐α‐D‐ erythro ‐pentofuranose ( 2 ) gave exclusively the corresponding blocked nucleosides with β‐anomeric configuration 3a and 3b , which on deprotection gave 1‐(2‐deoxy‐β‐D‐ erythro ‐pentofuranosyl) derivatives of 1a ( 3c ) and 1b ( 3d ). Functional group transformation of 3c and 3d provided a number of 2‐monosubstituted 4a‐c and 2,4‐disubstituted 4d‐f derivatives of 1‐(2‐deoxy‐β‐D‐ erythro ‐pentofuranosyl)pyrrole. Similar glycosylation of the sodium salt of 1a and 1b with 1‐chloro‐2,3,5‐tri‐ O ‐benzyl‐α‐D‐arabinofuranose ( 5 ) and further functional group transformation of the intermediate blocked nucleosides 6a and 6b provided 1‐β‐D‐arabinofuranosyl derivatives of pyrrole‐2‐carboxamide ( 7b ) and pyrrole‐2,4‐dicarboxamide ( 7d ). The synthetic utility of this glycosylation procedure for the preparation of 1‐β‐D‐ribofuranosylpyrrole‐2‐carbonitrile ( 12 ) has also been demonstrated by reacting the sodium salt of 1a with 1‐chloro‐2,3‐ O ‐isopropylidene‐5‐ O ‐( t ‐butyl)dimethylsilyl‐α‐D‐ribofuranose ( 10 ) and subsequent deprotection of the blocked intermediate 11 . This study provided a convenient route to the preparation of aromatic pyrrole nucleosides.