Probes for a Regulatory Site on the Nicotinic Acetylcholine Receptor-Channel. Synthesis of (±)-7-Debutylperhydrohistrionicotoxin, (±)-2-Depentyl-7-debutylperhydrohistrionicotoxin,and their Analogues

Reaction of glutarimide with pent-4-enylmagnesium bromide, followed by cyclization of intermediate ketoamide, and hydrolysis of the formates 10 and 13 led to the mixture of the hydroxylactams 11 (cis) and 14 (trans) which could be separated via their benzenecarbamates. Reduction of cis-hydroxylactam 11 with LiAlH₄ yielded 2-depentyl-7-debutylperhydrohistrionicotoxin ( 6 ), whereas reduction of trans-isomer 14 gave the epimeric alcohol 9 . cis-Hydroxylactam 11 was converted via thiolactam 17 and the methylthio derivative 18 to ketimine 19 which was reduced with NaBH₄ yielding a mixture of natural 4 and unnatural 7 , analogues of perhydrohistrionicotoxin ( 2 ). Reduction of 4 with H₂ in the presence of Pd/C yielded (±)-7-debutylperhydrohistrionicotoxin ( 5 ).