Total Synthesis and Electrophysiological Properties of Natural (−)‐Perhydrohistrionicotoxin, its Unnatural (+)‐Antipode and their 2‐Depentyl Analogs

Natural (−)‐perhydrohistrionicotoxin (6a), its unnatural (+)‐antipode 6b, (−)‐2‐depentylperhydrohistrionicotoxin (7a) and its (+)‐antipode 7b have been prepared and characterized. Kishi's lactam 8 reacted with optically active iso‐cyanates, and the mixture of diastereomeric carbamates so obtained was separated and hydrolyzed yielding the optical antipodes of Kishi's lactam in optically pure form. Reduction with LiAlH4 yielded the optically active 2‐depentyl analogs, while another sequence already developed in the racemic series afforded the natural toxin and its (+)‐antipode. Some electrophysiological properties of these compounds are presented.