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Probes for a Regulatory Site on the Nicotinic Acetylcholine Receptor‐Channel. Synthesis of (±)‐7‐Debutylperhydrohistrionicotoxin, (±)‐2‐Depentyl‐7‐debutylperhydrohistrionicotoxin, and their Analogues
Author(s) -
Gessner Wieslaw,
Takahashi Kimio,
Witkop Bernhard,
Brossi Arnold,
Albuquerque Edson X.
Publication year - 1985
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19850680106
Subject(s) - chemistry , bromide , hydrolysis , nicotinic acetylcholine receptor , alcohol , stereochemistry , nicotinic agonist , derivative (finance) , selective reduction , medicinal chemistry , organic chemistry , receptor , catalysis , biochemistry , financial economics , economics
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 LiAlH 4 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 NaBH 4 yielding a mixture of natural 4 and unnatural 7 , analogues of perhydrohistrionicotoxin ( 2 ). Reduction of 4 with H 2 in the presence of Pd/C yielded (±)‐7‐debutylperhydrohistrionicotoxin ( 5 ).