Synthesis of (-)-epibatidine and its derivatives from chiral allene-1,3-dicarboxylate esters.
(-)-Epibatidine, an excellent candidate of non-opioidal anesthesia, was formally synthesized in short steps from di-(l)-menthyl (R)-allene-1,3-dicarboxylate that was facilely prepared as a single isomer by means of crystallization-induced asymmetric transformation from a diastereomer mixture of (R)- and (S)-allene-1,3-dicarboxylates. Taking advantage of the chiral synthesis, derivatives of (-)-epibatidine were also prepared for targeting diagnostic agents that could bind nicotinic acetylcholine receptors (nAChRs) in the mammalian central nerve system.
Kimura
Hiroyuki
H
Department of Pharmaceutical Manufacturing Chemistry, 21st Century COE Program, Kyoto Pharmaceutical University, Misasagi, Japan.
Fujiwara
Toshio
T
Katoh
Takahiro
T
Nishide
Kiyoharu
K
Kajimoto
Tetsuya
T
Node
Manabu
M
D000466:Alkadienes / Q000737:chemistry*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis*; D003998:Dicarboxylic Acids / Q000737:chemistry*; D004952:Esters; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D018722:Nicotinic Agonists / Q000138:chemical synthesis*; D011725:Pyridines / Q000138:chemical synthesis*; D011978:Receptors, Nicotinic / Q000187:drug effects; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared
D000466:Alkadienes; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003998:Dicarboxylic Acids; D004952:Esters; D007202:Indicators and Reagents; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C025947:propadiene; C082748:epibatidine