Unified Total Synthesis of Madangamine Alkaloids
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- Suto Takahiro
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University
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- Yanagita Yuta
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University
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- Nagashima Yoshiyuki
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University
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- Takikawa Shinsaku
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University
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- Kurosu Yasuhiro
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University
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- Matsuo Naoya
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University
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- Miura Kazuki
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University
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- Simizu Siro
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University
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- Sato Takaaki
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University
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- Chida Noritaka
- Department of Applied Chemistry, Faculty of Science and Technology, Keio University
Abstract
<p>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 A–E. The synthetic madangamine alkaloids exhibited inhibitory activities against a variety of human cancer cell lines.</p>
Journal
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- Bulletin of the Chemical Society of Japan
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Bulletin of the Chemical Society of Japan 92 (3), 545-571, 2019-03-15
The Chemical Society of Japan
