Lactam Strategy Using Amide-Selective Nucleophilic Addition for Quick Access to Complex Amines: Unified Total Synthesis of Stemoamide-Type Alkaloids

Yasukazu Sugiyama, Yasuki Soda, Makoto Yoritate, Hayato Tajima, Yoshito Takahashi, Kana Shibuya, Chisato Ogihara, Takashi Yokoyama, Takeshi Oishi, Takaaki Sato, Noritaka Chida

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Our research group has been exploring a lactam strategy for the concise total synthesis of complex alkaloids. In this article, we report full details of the unified total synthesis of stemoamide-type alkaloids by chemoselective assembly of five-membered rings based on the lactam strategy. First, the concise and gram-scale synthesis of tricyclic stemoamide was achieved by vinylogous Michael addition-reduction sequence of an unsaturated γ-lactam with an unsaturated γ-lactone, followed by N-alkylation to form the seven-membered ring. From stemoamide as a common intermediate, chemoselective nucleophilic addition of unsaturated lactone derivatives provides tetracyclic natural products. While stemonine is obtained by an Ir-catalyzed lactam-selective reductive Mannich reaction, saxorumamide and isosaxorumamide are produced through the lactone-selective nucleophilic addition of the lithiated 2- silyl furan. The developed conditions for the lactam-selective nucleophilic reactions are highly general, and were found to be applicable to the total synthesis of pentacyclic stemocochinin and isostemocochinin. The strategy enables the concise and unified total synthesis of tricyclic, tetracyclic and pentacyclic stemoamide-type alkaloids within 12 steps from a commercially available compound.

Original languageEnglish
Pages (from-to)278-287
Number of pages10
JournalBulletin of the Chemical Society of Japan
Volume95
Issue number2
DOIs
Publication statusPublished - 2022

Keywords

  • Amide
  • Stemona alkaloid
  • Total synthesis

ASJC Scopus subject areas

  • Chemistry(all)

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