Practical Asymmetric Synthesis of Amathaspiramides B, D, and F

The practical asymmetric synthesis
of amathaspiramides B, D, and
F has been accomplished by utilizing an aza-Barbier allylation as
the key step to construct the common intermediate with two adjacent
stereocenters. A kinetically controlled cyclization to build the challenging
thermodynamically less stable 8R-hemiaminal moiety
is also important in the synthesis of amathaspiramide D. The route
is readily scalable, and gram quantity of the final product D has
been prepared.

本研究以氮杂Barbier烯丙基化反应（aza-Barbier allylation）为关键步骤构建含两个相邻手性中心的通用中间体，完成了阿马螺旋酰胺类（amathaspiramides）B、D、F的实用化不对称合成。在阿马螺旋酰胺D的合成中，通过动力学控制环化构建具有挑战性的热力学不稳定8R构型半缩醛基团，亦是该合成路线的关键环节。该合成方法具备良好的可放大性，已成功制备克级规模的最终产物D。