Nereus Pharmaceuticals, Inc., 10480 Wateridge Circle, San Diego, California 92121, USA.
J Org Chem. 2010 Jun 4;75(11):3882-5. doi: 10.1021/jo100432g.
Expedient access to a highly functionalized 2-pyrrolidinone (8), the gamma-lactam core of 20S proteasome inhibitor (-)-salinosporamide A (marizomib; NPI-0052; 1), using a regio- and stereoselective epoxide formation/reductive oxirane ring-opening strategy is presented. Notably, the sequential construction of the C-4, C-3, and C-2 stereocenters of 1 in a completely stereocontrolled fashion is a key feature of streamlining the synthesis of intermediate 12. A related strategy is also discussed.
本文介绍了一种通过区域和立体选择性环氧化物形成/还原环氧开环策略，来获得高度功能化的 2-吡咯烷酮（8），这是 20S 蛋白酶体抑制剂（-）-salinosporamide A（marizomib；NPI-0052；1）的γ-内酰胺核心。值得注意的是，通过连续构建中间体 12 的完全立体控制方式构建 1 的 C-4、C-3 和 C-2 立体中心，这是简化合成的关键特征。还讨论了一种相关策略。
