Stereoselective Transformation of Enantiopure Cyclohexenol into cis-Hydrindan. An Enantioselective Formal Total Synthetic Route to (+)-Pumiliotoxin C

摘要

Pumiliotoxin C (1) was originally isolated from the skin extracts of Dendrobates pumilio (a striking colored Panamanian poison arrow frog). X-ray analysis of the crystalline hydrochloride of 1 established the structure, and the absolute configuration (2S,4aS,5R,8aR) of this toxin was confirmed in 1977 by its total synthesis. Because of the scarcity of natural material (e.g., 15 mg of 1 from 250 frogs) coupled with the intriguing pharmacological properties, pumiliotoxin C (1) and gephy-rotoxin (2) (isolated from Columbian poison frog Dendrobates histrionicus) have proved to be challenges in organic synthesis. These alkaloids have in common the unusual cis-decahydroquinoline ring system with side-chain substituents at the C-2 and C-5 positions (the C-2 side chain of 2 being attached at nitrogen). Pumiliotoxin C (1) has served as a target for the synthesis of cis-decahydroquinoline alkaloids and has frequently been used to illustrate new methodologies for construction of the decahydroquinoline ring system.