Unified Total Synthesis of Madangamine Alkaloids

Takahiro Suto, Yuta Yanagita, Yoshiyuki Nagashima, Shinsaku Takikawa, Yasuhiro Kurosu, Naoya Matsuo, Kazuki Miura, Siro Simizu, Takaaki Satou, Noritaka Chida

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The full details of a unified total synthesis of madangamine alkaloids are disclosed. Our central strategy is based on the construction of a common ABCE-tetracyclic system, followed by the late-stage installation of various D-rings. The common intermediate is assembled through N-acyliminium cyclization of a propargylsilane, and formation of the (Z,Z)-skipped diene. Stereoselective synthesis of the (Z,Z)-skipped diene is especially challenging, and is accomplished by the combination of Z-selective hydroboration of the 1,1-disubstituted allene and subsequent Migita-Kosugi-Stille coupling. Macrocyclic alkylation enables the late-stage variation of the D-rings on the common tetracyclic intermediate, resulting in the collective total syntheses of madangamines AE. The synthetic madangamine alkaloids exhibited inhibitory activities against a variety of human cancer cell lines.

Original languageEnglish
Pages (from-to)545-571
Number of pages27
JournalBulletin of the Chemical Society of Japan
Volume92
Issue number3
DOIs
Publication statusPublished - 2019 Jan 1

Keywords

  • Madangamine
  • Skipped diene
  • Total synthesis

ASJC Scopus subject areas

  • Chemistry(all)

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