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

1 Citation (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

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Alkaloids
Cyclization
Alkylation
Cells

Keywords

  • Madangamine
  • Skipped diene
  • Total synthesis

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Suto, T., Yanagita, Y., Nagashima, Y., Takikawa, S., Kurosu, Y., Matsuo, N., ... Chida, N. (2019). Unified Total Synthesis of Madangamine Alkaloids. Bulletin of the Chemical Society of Japan, 92(3), 545-571. https://doi.org/10.1246/bcsj.20180334

Unified Total Synthesis of Madangamine Alkaloids. / Suto, Takahiro; Yanagita, Yuta; Nagashima, Yoshiyuki; Takikawa, Shinsaku; Kurosu, Yasuhiro; Matsuo, Naoya; Miura, Kazuki; Simizu, Siro; Satou, Takaaki; Chida, Noritaka.

In: Bulletin of the Chemical Society of Japan, Vol. 92, No. 3, 01.01.2019, p. 545-571.

Research output: Contribution to journalArticle

Suto T, Yanagita Y, Nagashima Y, Takikawa S, Kurosu Y, Matsuo N et al. Unified Total Synthesis of Madangamine Alkaloids. Bulletin of the Chemical Society of Japan. 2019 Jan 1;92(3):545-571. https://doi.org/10.1246/bcsj.20180334
Suto, Takahiro ; Yanagita, Yuta ; Nagashima, Yoshiyuki ; Takikawa, Shinsaku ; Kurosu, Yasuhiro ; Matsuo, Naoya ; Miura, Kazuki ; Simizu, Siro ; Satou, Takaaki ; Chida, Noritaka. / Unified Total Synthesis of Madangamine Alkaloids. In: Bulletin of the Chemical Society of Japan. 2019 ; Vol. 92, No. 3. pp. 545-571.
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