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Asymmetric Total Synthesis of Brasilicardins
Author(s) -
Yoshimura Fumihiko,
Itoh Ryusei,
Torizuka Makoto,
Mori Genki,
Tanino Keiji
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201811403
Subject(s) - intramolecular force , conjugate , chemistry , stereoselectivity , ring (chemistry) , total synthesis , stereochemistry , terpenoid , glycosylation , amino acid , combinatorial chemistry , organic chemistry , catalysis , biochemistry , mathematical analysis , mathematics
Brasilicardins, bacterial diterpenoid natural products that display highly potent immunosuppressive activity, are promising immunosuppressant drug candidates. Structurally, they can be described as hybrids of terpenoids, amino acids, and saccharides, and share a characteristic highly strained anti ‐ syn ‐ anti ‐fused perhydrophenanthrene terpenoid scaffold (ABC‐ring system) with two quaternary asymmetric carbon atoms. A unified and stereoselective total synthesis of all four brasilicardins has been designed based on the strategic use of an intramolecular conjugate addition. The ABC‐ring system was initially constructed with high stereocontrol by novel intramolecular conjugate additions of Weinreb amides and in situ generated ( Z )‐vinyl copper species. The late‐stage common intermediate was subjected to stereoselective installation of the amino acid component, followed by introduction of the saccharide unit via glycosylation to accomplish the total synthesis of brasilicardins A–D. Our synthesis offers opportunities to synthesize various brasilicardin analogues for biological and pharmacological investigations.

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