Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
School of Medicine, Keio University, 4-1-1, Hiyoshi, Kohoku-ku, Yokohama 223-8521, Japan.
Org Lett. 2020 Oct 2;22(19):7502-7507. doi: 10.1021/acs.orglett.0c02697. Epub 2020 Sep 22.
The collective synthesis of pentacyclic stemoamide-type alkaloids is recognized as a daunting task despite high demand for a comprehensive biological profiling of these natural products. In this Letter, we report a unified synthesis of seven pentacyclic alkaloids and two unnatural derivatives. The keys to success are (1) the chemoselective assembly of four five-membered building blocks, (2) the direct oxidation of pyrrolidine natural products to pyrrole derivatives, and (3) the stereodivergent construction of totally E- or Z-substituted butenolides.
尽管对这些天然产物进行全面的生物分析有很高的需求，但五环[C]甾族酰胺型生物碱的集体合成仍然是一项艰巨的任务。在这封信中，我们报告了七种五环生物碱和两种非天然衍生物的统一合成。成功的关键是：（1）四个五元构建块的化学选择性组装，（2）吡咯烷天然产物的直接氧化为吡咯衍生物，（3）完全 E-或 Z-取代丁烯内酯的立体发散性构建。
