A facile and improved synthesis of tubercidin and certain related pyrrolo[2,3‐<i>d</i>]pyrimidine nucleosides by the stereospecific sodium salt glycosylation procedure

Abstract

Abstract A simple synthesis of tubercidin ( 1 ), 7‐deazaguanosine ( 2 ) and 2′‐deoxy‐7‐deazaguanosine ( 14 ) has been accomplished using the sodium salt glycosylation procedure. Reaction of the sodium salt of 4‐chloro‐ and 2‐amino‐4‐chloro‐pyrrolo[2,3‐ d ]pyrimidine, 3 and 4 , respectively, with 1‐chloro‐2,3‐ 0 ‐isopropylidene‐5‐ 0 ‐( t ‐butyl)dimethylsilyl‐α‐D‐ribofuranose ( 5 ) gave the corresponding protected nucleosides 6n and 7 with β‐anomeric configuration. Deprotection of 6 provided 8 , which on heating with methanolic ammonia gave tubercidin ( 1 ) in excellent yield. Functional group transformation of 7 , followed by deisopropylidenation gave 2‐aminotubercidin ( 10 ) and 2‐amino‐7‐β‐D‐ribofuranosylpyrrolo[2,3‐ d ]pyrimidine‐4(3 H )‐thione ( 11 ). Treatment of 7 with 1 N sodium methoxide followed by exposure to aqueous trifluoroacetic acid, and ether cleavage furnished 7‐deazaguanosine ( 2 ). 2′‐Deoxy‐7‐deazaguanosine ( 14 ) and 2′‐deoxy‐7‐deaza‐6‐thioguano‐sine ( 18 ) were also prepared by using similar sequence of reactions employing 4 and 1‐chloro‐2‐deoxy‐3,5‐di‐ O‐p ‐toluoyl‐α‐D‐ erythro ‐pentofuranose ( 15 ).