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

Authors :
Sara Mazeh
M. Dolores Garcia-Fernandez
Barbara Pelletier
Christophe Moreau
Philippe Delair
Département de pharmacochimie moléculaire (DPM)
Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Institut de biologie structurale (IBS - UMR 5075)
Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)
Direction de Recherche Fondamentale (CEA) (DRF (CEA))
Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA))
Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)
Labex Arcane CBH-EUR-GS
Mass spectrometry
Animal facility
ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)
ANR-15-IDEX-0002,UGA,IDEX UGA(2015)
Source :
Organic & Biomolecular Chemistry, Organic & Biomolecular Chemistry, 2023, 21 (4), pp.817-822. ⟨10.1039/d2ob01723g⟩
Publication Year :
2023

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.

Details

ISSN :
14770539 and 14770520
Database :
OpenAIRE
Journal :
Organicbiomolecular chemistry
Accession number :
edsair.doi.dedup.....8f60e253d468538821f50344d1587ff1
Full Text :
https://doi.org/10.1039/d2ob01723g⟩