School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, U.K.
J Am Chem Soc. 2022 May 11;144(18):7995-8001. doi: 10.1021/jacs.2c03192. Epub 2022 May 2.
Bastimolide B is a polyhydroxy macrolide isolated from marine cyanobacteria displaying antimalarial activity. It features a dense array of hydroxylated stereogenic centers with 1,5-relationships along a hydrocarbon chain. These 1,5-polyols represent a particularly challenging motif for synthesis, as the remote position of the stereocenters hampers stereocontrol. Herein, we present a strategy for 1,5-polyol stereocontrolled synthesis based on iterative boronic ester homologation with enantiopure magnesium carbenoids. By merging boronic ester homologation and transition-metal-catalyzed alkene hydroboration and diboration, the acyclic backbone of bastimolide B was rapidly assembled from readily available building blocks with full control over the remote stereocenters, enabling the total synthesis to be completed in 16 steps (LLS).
巴斯蒂莫利德 B 是一种从海洋蓝藻中分离出来的多羟基大环内酯，具有抗疟活性。它具有密集的羟化立体中心阵列，沿着烃链具有 1,5-关系。这些 1,5-多元醇代表了合成的特别具有挑战性的基序，因为立体中心的远程位置阻碍了立体控制。在这里，我们提出了一种基于具有手性纯镁卡宾的硼酸酯同系化的 1,5-多元醇立体控制合成策略。通过合并硼酸酯同系化和过渡金属催化的烯烃硼氢化和二硼化，从易得的构建块中快速组装了巴斯蒂莫利德 B 的无环骨架，完全控制了远程立体中心，使总合成可以在 16 步（LLS）内完成。
