Unified Total Synthesis of Stemoamide-Type Alkaloids by Chemoselective Assembly of Five-Membered Building Blocks

• DOI: 10.1021/jacs.7b10944
• Publication Date: 2017-11-28T04:08:19Z
• Authors: Makoto Yoritate; Yoshito Takahashi; Hayato Tajima; Chisato Ogihara; Takashi Yokoyama; Yasuki Soda; Takeshi Oishi; Takaaki Sato; Noritaka Chida
• Keywords: Alkaloids; Molecular Structure; Heterocyclic Compounds, 3-Ring; 01 natural sciences; 0104 chemical sciences

A unified total synthesis of stemoamide-type alkaloids is reported. Our synthetic approach features the chemoselective convergent assembly of five-membered building blocks via stemoamide as the common precursor to tetracyclic natural products. The synthesis consists of two successive coupling reactions of the three five-membered building blocks. The first coupling reaction is the vinylogous Michael addition/reduction sequence, which enables the gram-scale synthesis of stemoamide. The second coupling reaction is a chemoselective nucleophilic addition to stemoamide. While the lactone-selective nucleophilic addition to stemoamide affords saxorumamide and isosaxorumamide, the lactam-selective reductive nucleophilic addition leads to the formation of stemonine. Both chemoselective nucleophilic additions enable direct modification of stemoamide, resulting in highly concise and efficient total syntheses of the stemoamide-type alkaloids.