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 C 2 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 (−)-1, 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]