Organic Chemistry Section, Facultat de Química, Universitat de Barcelona , Diagonal 645, 08028 Barcelona, Catalonia, Spain.
J Org Chem. 2017 Oct 20;82(20):11021-11034. doi: 10.1021/acs.joc.7b01973. Epub 2017 Oct 6.
A formal total synthesis of the cytotoxic macrolide amphidinolide E is reported. The strategic steps are three Julia-Kocienski reactions (J-K), for the formation of the C5-C6, C9-C10, and C17-C18 double bonds, a Suzuki-Molander C21-C22 bond formation reaction, and a Kita-Trost macrolactonization. The "instability" of the two dienic systems and of the stereocenter at C2 (allylic methine, α to the carboxy group) and the protecting groups at C17-OH and C18-OH have posed difficult challenges. Each Julia-Kocienski olefination has been systematically optimized to provide the highest possible E/Z ratios.
报道了细胞毒性大环内酯安非丁醇 E 的全合成。该策略的关键步骤包括三个 Julia-Kocienski 反应（J-K），用于形成 C5-C6、C9-C10 和 C17-C18 双键，一个 Suzuki-Molander C21-C22 键形成反应，以及一个 Kita-Trost 大环内酯化反应。两个双键体系以及 C2（偕二烯丙基次甲基，位于羧基的 α 位）和 C17-OH、C18-OH 上保护基的立体中心的“不稳定性”带来了艰巨的挑战。每个 Julia-Kocienski 烯烃化反应都经过系统优化，以提供尽可能高的 E/Z 比值。
