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Total synthesis of the natural (-)-205B alkaloid and its activity toward α7 nAChRs.

ABSTRACT: A new approach to the synthesis of the (-)-205B alkaloid is described in this paper. This work is characterised by the development of an efficient chirality transfer through a silyl tethered intramolecular alkylation reaction, an unprecedented tandem highly selective iridium catalyzed partial reduction of lactam coupled with an acid promoted aza-Prins reaction, and an almost complete stereochemical control in Shenvi's radical hydrogen atom transfer on an exocyclic methylene. The second part of this work demonstrates the positive allosteric behavior of this natural alkaloid toward α7 nAChRs, in contrast to the reported inhibitory effect of the unnatural enantiomer.

SUBMITTER: Mazeh S

PROVIDER: S-EPMC9972826 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Total synthesis of the natural (-)-205B alkaloid and its activity toward α7 nAChRs.

Mazeh Sara S Garcia-Fernandez M Dolores MD Pelletier Barbara B Moreau Christophe C Delair Philippe P

Organic & biomolecular chemistry 20230125 4

A new approach to the synthesis of the (-)-205B alkaloid is described in this paper. This work is characterised by the development of an efficient chirality transfer through a silyl tethered intramolecular alkylation reaction, an unprecedented tandem highly selective iridium catalyzed partial reduction of lactam coupled with an acid promoted aza-Prins reaction, and an almost complete stereochemical control in Shenvi's radical hydrogen atom transfer on an exocyclic methylene. The second part of t ...[more]

PMID: 36601968

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