TY - JOUR
T1 - Unified Total Synthesis of Madangamine Alkaloids
AU - Suto, Takahiro
AU - Yanagita, Yuta
AU - Nagashima, Yoshiyuki
AU - Takikawa, Shinsaku
AU - Kurosu, Yasuhiro
AU - Matsuo, Naoya
AU - Miura, Kazuki
AU - Simizu, Siro
AU - Sato, Takaaki
AU - Chida, Noritaka
N1 - Funding Information:
This research was supported by the Otsuka Pharmaceutical Co. Award in Synthetic Organic Chemistry, Japan, and a JSPS fellowship to T. Suto (18J11234). We thank Prof. Raymond J. Andersen, The University of British Columbia, Canada for giving 1H and 13C NMR spectra of madangamine alkaloids, and precious advice. Synthetic assistance from T. Matsumoto, S. Hiraoka, Y. Komiya and A. Azuma is gratefully acknowledged.
Publisher Copyright:
© 2019 The Chemical Society of Japan. All rights reserved.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Madangamine
KW - Skipped diene
KW - Total synthesis
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U2 - 10.1246/bcsj.20180334
DO - 10.1246/bcsj.20180334
M3 - Article
AN - SCOPUS:85063738412
SN - 0009-2673
VL - 92
SP - 545
EP - 571
JO - Bulletin of the Chemical Society of Japan
JF - Bulletin of the Chemical Society of Japan
IS - 3
ER -
