Asymmetric Total Synthesis of Brasilicardins. Issue 52 (28th November 2018)

• Record Type: Journal Article
• Authors: Yoshimura, Fumihiko; Itoh, Ryusei; Torizuka, Makoto; Mori, Genki; Tanino, Keiji
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 52(2018)
• Page Start: 17161
• Page End: 17167
• Publication Date: 2018-11-28
• Subjects: brasilicardins -- Michael addition -- natural products -- quaternary stereocenters -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201811403
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : One approach, four targets : The asymmetric total synthesis of brasilicardin A, a hybrid natural product with highly potent immunosuppressive activity, has been developed. The synthesis features a Michael addition based strategy for the stereoselective formation of the highly strained anti‐syn‐anti ‐fused perhydrophenanthrene skeleton, and brasilicardins B–D are also synthesized based on the unified approach.