Department of Chemistry and Department of Medicinal Chemistry, Purdue University , 560 Oval Drive, West Lafayette, Indiana 47907, United States.
Org Lett. 2016 Jul 1;18(13):3274-7. doi: 10.1021/acs.orglett.6b01523. Epub 2016 Jun 22.
Both epimers at C-21 in the proposed structure of (+)-callyspongiolide have been synthesized in a convergent and enantioselective manner. The 14-membered macrolide with a sensitive C2-C3 cis-olefin functionality was installed by a Yamaguchi macrolactonization of hydroxyl alkynoic acid followed by hydrogenation over Lindlar's catalyst. The C5 methyl stereocenter was constructed by a ring-closing olefin metathesis followed by addition of methyl cuprate to an α,β-unsaturated δ-lactone. Other key reactions are chiral Corey-Bakshi-Shibata (CBS) reduction and Sonogashira coupling to conjoin the macrocyclic core and side chain.
所提出的 (+)-卡里脂肽结构中 C-21 位的两个差向异构体均以收敛和对映选择性的方式合成。通过 Yamaguchi 大环内酯化羟基炔酸,随后在 Lindlar 催化剂上氢化,引入具有敏感 C2-C3 顺式烯烃官能团的 14 元大环内酯。通过闭环烯烃复分解反应,然后向 α,β-不饱和 δ-内酯中添加甲基铜试剂,构建 C5 甲基立体中心。其他关键反应包括手性 Corey-Bakshi-Shibata (CBS) 还原和 Sonogashira 偶联,以连接大环核心和侧链。