Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany).
Angew Chem Int Ed Engl. 2014 Apr 14;53(16):4217-21. doi: 10.1002/anie.201400605. Epub 2014 Mar 12.
A concise synthesis of the putative structure assigned to the highly cytotoxic marine macrolide mandelalide A (1) is disclosed. Specifically, an iridium-catalyzed two-directional Krische allylation and a cobalt-catalyzed carbonylative epoxide opening served as convenient entry points for the preparation of the major building blocks. The final stages feature the first implementation of terminal-acetylene metathesis into natural product synthesis, which is remarkable as this class of substrates was beyond reach until very recently; key to success was the use of the highly selective molybdenum alkylidyne complex 42 as the catalyst. Although the constitution and stereochemistry of the synthetic samples are unambiguous, the spectra of 1 as well as of 11-epi-1 deviate from those of the natural product, which implies a subtle but deep-seated error in the original structure assignment.
本文披露了一种将高细胞毒性海洋大环内酯 mandelalide A（1）假定结构进行简洁合成的方法。具体而言，铱催化的双向 Krische 烯丙基化和钴催化的羰基化环氧化物开环为主要构建块的制备提供了便利的切入点。最后阶段的特点是首次将末端炔烃复分解反应应用于天然产物合成，这是显著的，因为直到最近，这类底物才难以实现；成功的关键是使用高选择性的钼烷基化物复合物 42 作为催化剂。尽管合成样品的结构和立体化学是明确的，但 1 以及 11-epi-1 的光谱与天然产物的光谱不同，这意味着原始结构分配中存在微妙但深层次的错误。
