A novel enantioselective synthesis of (S)-(-)- and (R)-(+)-nornicotine via alkylation of a chiral 2-hydroxy-3-pinanone ketimine template.
An asymmetric synthesis of the optically pure isomers of the minor tobacco alkaloid and CNS nicotine metabolite, nornicotine, has been achieved with moderately high optical purity. The synthetic pathway involves alkylation of a chiral ketimine, prepared from either 1R,2R,5R-(+)- or 1S,2S,5S-(-)-2-hydroxy-3-pinanone and 3-(aminomethyl)pyridine with 3-bromopropan-1-ol. After cleavage of the respective C-alkylated ketimines with NH2OH.HCl, and treatment of the resulting amino alcohols with HBr, followed by base-catalyzed intramolecular ring closure, (S)-(-)-nornicotine and (R)-(+)-nornicotine were obtained with ee values of 91% and 81%, respectively.
Swango
J H
JH
College of Pharmacy, Department of Pharmaceutical Sciences, University of Kentucky, Lexington 40536-0082, USA.
Bhatti
B S
BS
Qureshi
M M
MM
Crooks
P A
PA
D000478:Alkylation; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009538:Nicotine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D011725:Pyridines; D013237:Stereoisomerism
C118834:2-hydroxy-3-pinanone ketimine; D007202:Indicators and Reagents; D011725:Pyridines; D009538:Nicotine; C005311:nornicotine