Total Synthesis of Pinnatoxins A and G and Revision of the Mode of Action of Pinnatoxin A

• DOI: 10.1021/ja201254c
• Publication Date: 2011-06-06T23:06:29Z
• Authors: Romulo Araoz; Denis Servent; Jordi Molgó; Bogdan I. Iorga; Carole Fruchart-G...; Evelyne Benoit; Zhenhua Gu; Craig Stivala; Armen Zakarian
• Keywords: Mode of Action; Mode (computer interface)

Pinnatoxins belong to an emerging class of potent marine toxins the cyclic imine group. Detailed studies their biological effects have been impeded by unavailability complex natural product from sources. This work describes development a robust, scalable synthetic sequence relying on convergent strategy that delivered sufficient amount toxin for detailed and its commercialization use other research groups regulatory agencies. A central transformation in synthesis is highly diastereoselective Ireland–Claisen rearrangement α,α-disubstituted allylic ester based unique mode stereoselective enolization through chirality match between substrate lithium amide base. With pinnatoxin A, study has performed provides conclusive evidence action as inhibitor nicotinic acetylcholine receptors selective human neuronal α7 subtype. The comprehensive electrophysiological, biochemical, computational support view spiroimine subunit pinnatoxins critical blocking receptor subtypes, evidenced analyzing effect analogue containing open form ring. Our paved way production certified standards be used mass-spectrometric determination these matrices tests detect contaminated shellfish.