Asymmetric Total Synthesis of Brasilicardins
| Autor: | Makoto Torizuka, Fumihiko Yoshimura, Ryusei Itoh, Genki Mori, Keiji Tanino |
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| Rok vydání: | 2018 |
| Předmět: |
Glycosylation
natural products Stereochemistry Molecular Conformation 010402 general chemistry 01 natural sciences Catalysis chemistry.chemical_compound Michael addition total synthesis chemistry.chemical_classification 010405 organic chemistry Chemistry Total synthesis Stereoisomerism General Medicine General Chemistry 0104 chemical sciences Amino acid Aminoglycosides Asymmetric carbon Intramolecular force Michael reaction quaternary stereocenters Stereoselectivity Diterpenes brasilicardins Conjugate |
| Zdroj: | Angewandte Chemie (International ed. in English). 57(52) |
| ISSN: | 1521-3773 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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