烟碱激动剂
乙酰胆碱受体
化学
乙酰胆碱
受体
药理学
神经科学
生物化学
生物
作者
Keisuke Nishikawa,Yoshiki Ono,Shizuka Mori,Koichi Takayama,Makoto Ihara,Kazuhiko Matsuda,Yoshiki Morimoto
标识
DOI:10.1021/acs.joc.3c02988
摘要
Histrionicotoxin (HTX) alkaloids, which are isolated from Colombian poison dart frogs, are analgesic neurotoxins that modulate nicotinic acetylcholine receptors (nAChRs) as antagonists. Perhydrohistrionicotoxin (pHTX) is the potent synthetic analogue of HTX and possesses a 1-azaspiro[5.5]undecane skeleton common to the HTX family. Here, we show for the first time the divergent nine-step synthesis of pHTX and its three stereoisomers from the known aldehyde through a one-step construction of the 1-azaspiro[5.5]undecane framework from a linear amino ynone substrate. Surprisingly, some pHTX diastereomers exhibited antagonistic activities on the chicken α4β2-neuronal nAChRs that were more potent than pHTX.
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