Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
Org Lett. 2011 Jun 17;13(12):3028-31. doi: 10.1021/ol200886j. Epub 2011 May 17.
A concise and stereoselective total synthesis of (-)-salinosporamide A (1), a potent inhibitor of the 20S proteasome that is in clinical development as an anticancer drug candidate, has been accomplished in 14 steps with 19% overall yield from 4-pentenoic acid. Our synthesis features a stereoselective alkylation utilizing a chiral auxiliary, formation of a pyrrolidine unit, and oxidation of the pyrrolidine to a γ-lactam. To demonstrate the scalability of our synthesis, (-)-salinosporamide A has been synthesized on a gram scale.
已完成（-）-盐诺博酰胺 A（1）的简洁和立体选择性全合成，1 是一种强效的 20S 蛋白酶体抑制剂，目前作为抗癌药物候选物处于临床开发阶段，从 4-戊烯酸以 19%的总收率经 14 步反应得到。我们的合成采用了立体选择性烷基化反应，利用手性辅助剂、形成吡咯烷单元以及将吡咯烷氧化为γ-内酰胺。为了证明我们的合成的可扩展性，已在克级规模上合成了（-）-盐诺博酰胺 A。
