Enantioselective total synthesis of (+)- and (-)-pyrrolidine 197B, a new class of alkaloid from the dendrobatid poison frog: assignment of the absolute configuration

Abstract

Enantioselective total synthesis of both enantiomers of pyrrolidine 197B (1), a new class of dendrobatid alkaloid, is described. The synthesis begins with the C2 symmetric S, S or R, R diepoxides 4, derived from (S, S)-1, 2, 5, 6-hexanetetraol (2) as a single common chiral synthon, and involves pyrrolidine formation via the cyclic sulfonates to afford (+)- or (−)-l, respectively. The (+) and (−) enantiomers of 1 were converted to the corresponding N-benzoyl derivatives (+)-27 and (−)-27, which were directly compared with 27 derived from natural 1 by HPLC using a Chiralcel column. This comparison established the absolute stereochemistry of the natural enantiomer of pyrrolidine 197B as 2S.5S [(+)-1]. © 1991, American Chemical Society. All rights reserved.