Synthesis of Poison Frog Alkaloids : Novel, Potent and Subtype-selective Blockers of Neuronal Nicotinic Acetylcholine Receptors

Abstract

This article describes the synthesis of poison frog alkaloids using the highly stereoselective conjugate addition reaction as the key step. First total synthesis of the alkaloid 223A has been achieved. The proposed structure for natural 223A was revised and the relative stereostructure was determined by this total synthesis. First total syntheses of tricyclic alkaloid 205B and quinolizididne 207I have been achieved, and the absolute stereochemistry of both natural products was determined by these total syntheses. Investigations of the inhibitory effects of synthetic poison frog alkaloids on neuronal nicotinic acetylcholine receptors have also been conducted, and we found the 5, 8-disubstituted indolizidine 235B'is a promising lead compound for the drug design to treat autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).