A concise synthesis of physostigmine from skatole and activated aziridine via alkylative cyclization.
A concise synthetic route to physostigmine has been developed, where the key step relies on the alkylative cyclization of 1,3-dimethylindole with (Z)-aziridine catalyzed by Sc(OTf)3 and TMSCI in dichloromethane at -30 degrees C, to give 8 in 90% yield, which, in turn, can be readily converted into physostigmine.
Nakagawa
M
M
Faculty of Pharmaceutical Sciences, Chiba University, Japan. nakagawa@p.chiba-u.ac.jp
Kawahara
M
M
D000478:Alkylation; D001388:Aziridines / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis*; D003500:Cyclization; D007202:Indicators and Reagents; D010830:Physostigmine / Q000138:chemical synthesis*; D012862:Skatole / Q000737:chemistry*; D012997:Solvents
D001388:Aziridines; D002800:Cholinesterase Inhibitors; D007202:Indicators and Reagents; D012997:Solvents; D010830:Physostigmine; D012862:Skatole