비전형적 뉴크레오사이드와 C-뉴크레오사이드의 합성 및 약효검색

Abstract

본 논문에서는 신규 cyclohexenyl carbocyclic nucleoside 및 mercaptophenyl car-bocyclic C-nucleoside를 합성하고 이들의 약효를 검색하고자 하였다. carbocyclic nu-cleoside 및 C-nucleoside는 화학요법 영역에서 높은 항바이러스 활성을 가지고 있다. 본 연구 중 cyclohexenyl carbocyclic nucleoside는 입체선택적인 합성방법으로 합성하였으며 그의 racemic에 대하여 기술하였다. 우선, Mitsunobu 조건하에서 6-chloro-purine을 축합시켜 최종화합물 17을 합성하였고, 또 [3,3]-sigmatropic rearrangement, ring-closing metathesis (RCM) 등 일련의 반응을 수행하여 중간생성물 27을 합성하고 Friedel-Crafts alkylation 시켜서 최종화합물인 mercaptophenyl carbocyclic C-nucleoside 31을 합성하였다.|The synthesis of cyclohexenyl carbocyclic nucleoside and carbocyclic C-nucleoside analogues has been inspired by their chemical and enzymatic stability. Cyclohexenyl carbocyclic nucleoside describes a racemic and stereoselective synthetic route for a novel cyclohexenyl carbocyclic adenine analogue. The required stereochemistry of the target compound was controlled using a stereoselective glycolate Claisen rearrangement followed by α-Chelated carbonyl addition. 6-Chloropurine analogue was achieved using a Mitsunobu condition, and further modifications of the corres- ponding heterocycle gave the target cyclohexenyl nucleoside 17. And non-classical mercaptophenyl carbocyclic C-nucleoside was synthesized via a cyclopentenol intermediate 27, which was prepared using a sequential [3,3]-sigmatropic rearrangement and ring-closing metathesis (RCM). Friedel-Crafts alkylation was then used to couple the thiophenol.