Nshimiyimana Robert, Lam Ting Fung, Aggarwal Shubhangi, Serhan Charles N, Petasis Nicos A
Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California Los Angeles California 90089 USA
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts 02115 USA.
RSC Adv. 2022 Apr 19;12(19):11613-11618. doi: 10.1039/d2ra01537d. eCollection 2022 Apr 13.
The first total convergent synthesis of 4(),5()-oxido-17()-hydroxy-6(),8(),10(),13(),15(),19()-docosahexaenoic acid (1) is described. The reported synthesis led to confirmation of the native epoxydocosahexaenoic acid as the biosynthetic precursor of lipid mediators resolvin D3 and resolvin D4. These potent enzymatic products of docosahexaenoic acid (DHA) are important signaling molecules in the resolution of inflammation. A stereocontrolled and chiral pool-based synthetic strategy was employed, with key features including epoxide transposition under basic conditions to form the oxirane ring, and a -selective Wittig reaction to secure the target docosahexaenoate backbone.
本文描述了4(),5()-环氧-17()-羟基-6(),8(),10(),13(),15(),19()-二十二碳六烯酸(1)的首次全合成。所报道的合成方法证实了天然环氧二十二碳六烯酸是脂质介质消退素D3和消退素D4的生物合成前体。这些二十二碳六烯酸(DHA)的高效酶促产物是炎症消退过程中的重要信号分子。采用了一种基于立体控制和手性池的合成策略，其关键特征包括在碱性条件下进行环氧化物转位以形成环氧乙烷环，以及通过α-选择性维蒂希反应来构建目标二十二碳六烯酸酯主链。
