氮端Fmoc保护的Statine类化合物的合成  

Synthesis of N-Fmoc Statine and Its Analogue

作　　者：肖坤[1] 王昕[1] 沈竞康[1] 

机构地区：[1]中国科学院上海生命科学院上海药物研究所新药研究国家重点实验室

出　　处：《合成化学》2006年第4期375-377,394,共4页Chinese Journal of Synthetic Chemistry

基　　金：国家"863"高科技基金资助项目(2004AA2Z3781);国家自然科学基金资助项目(30230400);国家基础研究重大专项基金资助项目(2004GB518907)

摘　　要：采用DIC为羧基活化剂成功实现氮端Fmoc保护的亮氨酸与Meldrum’s acid反应,生成1,3-二氧杂环己烷-4,6-二酮衍生物,后者无需纯化直接在乙酸乙酯中加热回流,自动关环产生Tetramic acid化合物。Tetra-mic acid用NaBH4还原得到4-羟基-吡咯烷酮类衍生物,继之水解,即得氮端Fmoc保护的Statine(6a)。立体化学研究证明,6a具有3S,4S结构,且手性纯度很高。Employing DIC as carboxyl activating agent, N-Fmoc leucine reacted smoothly with Meldrum＇s acid to produce 1,3-dioxane-4,6-dione derivative, which was converted directly to tertramic acid by reflux with ethyl acetate without further purification. The resulting tetramic acid was reduced by NaBH4 to afford 4-hydroxy-pyrrolidine-2-one derivative, which was further hydrolyzed in acid media to yield the desired N-Fmoc Statine. The chirality of the synthesized N-Fmoc Statine was also well studied.

关 键 词：STATINE 活化剂 手性 合成 

分 类 号：O623.6[理学—有机化学]