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

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 reacti...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2017-12, Vol.139 (50), p.18386-18391
Main Authors: Yoritate, Makoto, Takahashi, Yoshito, Tajima, Hayato, Ogihara, Chisato, Yokoyama, Takashi, Soda, Yasuki, Oishi, Takeshi, Sato, Takaaki, Chida, Noritaka
Format: Article
Language:English
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Summary: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.7b10944