6,6-Spiroimine analogs of (-)-gymnodimine A: synthesis and biological evaluation on nicotinic acetylcholine receptors. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Organic & Biomolecular Chemistry Année : 2011

6,6-Spiroimine analogs of (-)-gymnodimine A: synthesis and biological evaluation on nicotinic acetylcholine receptors.

Résumé

Simple models of the spiroimine core of (-)-gymnodimine A have been synthesized in racemic and optically active forms. The quaternary carbon of the racemic spiroimines was created by Michael addition of a β-ketoester to acrolein, whereas the asymmetric allylic alkylation of the same β-ketoester was used to access the spiroimines in an enantioselective fashion. Both racemic and enantio-enriched mixtures were tested for their biological activities on Xenopus oocytes either expressing (human α4β2) or having incorporated (Torpedoα1(2)βγδ) nicotinic acetylcholine receptors (nAChRs). These spiroimine analogs of (-)-gymnodimine A inhibited acetylcholine-evoked nicotinic currents, but were less active than the phycotoxin. Our results reveal that the 6,6-spiroimine moiety is important for the blockade of nAChRs and support the hypothesis that it is one of the pharmacophores of this group of toxins.
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Dates et versions

hal-00637236 , version 1 (31-10-2011)

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Citer

Leslie Duroure, Thierry Jousseaume, Rómulo Aráoz, Elvina Barré, Pascal Retailleau, et al.. 6,6-Spiroimine analogs of (-)-gymnodimine A: synthesis and biological evaluation on nicotinic acetylcholine receptors.. Organic & Biomolecular Chemistry, 2011, 9 (23), pp.8112-8. ⟨10.1039/c1ob06257c⟩. ⟨hal-00637236⟩
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