Naoki Toyooka
University of Toyama, Japan
Biography
To date, over 800 lipophilic alkaloids representing more than 20 structural classes have been detected from the skin extracts of neotropical poison frogs. The 2,5-disubstituted decahydroquinolines are represented one of the major classes, and the structural diversity and pharmacological activity associated with this class of alkaloids have stimulated synthetic activity in numerous groups. We report here the first total synthesis of the decahydroquinoline type poison-frog alkaloid cis-211A along with ent-cis-195A. The synthesis began with known piperidine 16, which was converted to aminoester 2 in 3 steps. Michael-type conjugate addition reaction of 2 provided the adduct 3 in high yield as a single stereoisomer. The ester 3 was transformed into the keto-aldehyde 4, which was subjected to an intermolecular aldol-type cyclization to afford the cis-fused enone 5 as a single isomer. The conjugate addition reaction of 5 followed by treatment of the resulting enolate with Comins’ reagent gave rise to the common and key intermediate of enol triflates 6. Synthesis of ent-cis-195A was achieved from 6 in 2 steps, and the first total synthesis of cis-211A was also completed from 6 in 5 steps as shown in Scheme1. Details of the synthetic process synthesis and their evaluation of the nicotinic acetylcholine receptors and inhibitory effect on [3H] nicotine uptake by TR-BBB13 cells of both synthetic alkaloids will be reported.
Abstract
Abstract : Total syntheses and their biological evaluation of poison-frog alkaloids ent-cis-195A and cis-211A