The School of Pharmaceutical Sciences & The Comprehensive AIDS Research Center, Tsinghua University , Beijing 100084, China.
Institute of Organic Chemistry, RWTH Aachen University , Landoltweg 1, 52074 Aachen, Germany.
J Am Chem Soc. 2018 Feb 7;140(5):1937-1944. doi: 10.1021/jacs.7b12903. Epub 2018 Jan 24.
The Plakortin polyketides represent a structurally and biologically fascinating class of marine natural products. Herein, we report a unified strategy that enables the divergent syntheses of various Plakortin polyketides with high step-economy and overall efficiency. As proof-of-concept cases, the enantioselective total syntheses of (+)-hippolachnin A, (+)-gracilioether A, (-)-gracilioether E, and (-)-gracilioether F have been accomplished based on a series of bio-inspired, rationally designed, or serendipitously discovered transformations, which include (1) an organocatalytic asymmetric 1,4-conjugate addition to assemble the common chiral γ-butenolide intermediate enroute to all of the aforementioned targets, (2) a challenging biomimetic [2+2] photocycloaddition to forge the oxacyclobutapentalene core of (+)-hippolachnin A, (3) a [2+2] photocycloaddition followed by one-pot oxidative cleavage of methyl ether/Baeyer-Villiger rearrangement to access (-)-gracilioether F, and (4) an unprecedented hydrogen-atom-transfer-triggered oxygenation of vinylcyclobutane to afford (+)-gracilioether A and (-)-gracilioether E in one pot.
Plakortin 聚酮类化合物代表了一类具有结构和生物意义的海洋天然产物。在此，我们报告了一种统一的策略，能够以高经济性和整体效率来实现各种 Plakortin 聚酮类化合物的发散合成。作为概念验证案例，基于一系列受生物启发、合理设计或偶然发现的转化，完成了 (+)-hippolachnin A、(+)-gracilioether A、(-)-gracilioether E 和 (-)-gracilioether F 的对映选择性全合成，这些转化包括：(1) 有机催化不对称 1,4-共轭加成，以组装常见的手性 γ-丁烯内酯中间体，从而合成所有上述目标化合物；(2) 具有挑战性的仿生 [2+2] 光环加成反应，以构建 (+)-hippolachnin A 的氧杂环丁烷并五元环核心；(3) [2+2] 光环加成反应，随后一锅氧化裂解甲醚/Baeyer-Villiger 重排反应，以获得 (-)-gracilioether F；(4) 前所未有的氢原子转移引发的乙烯基环丁烷氧化反应，一锅法合成 (+)-gracilioether A 和 (-)-gracilioether E。
