A reappraisal of the stereoselective metabolism of nicotine to nicotine-1'-N-oxide.
1. The cis and trans 1'-N-oxide metabolites of (2'R)-(+)-nicotine have the absolute configuration (1'S; 2'R) and (1'R; 2'R), respectively, and not the reverse as previously published. 2. Reinterpretation of metabolic data in the light of this reassignment reveals that N-oxidation of nicotine leads preferentially to the (1'R)-N-oxide, with little dependence on the configuration of the 2'-centre. 3. It is proposed that (2'S)-(-)-nicotine and (2'R)-(+)-nicotine bind to the same enzymic site by two distinct modes of binding; each of these modes involves the more basic centre (in this case the pyrrolidine ring) as the governing binding moiety.
D000818:Animals; D006224:Cricetinae; D003497:Cyclic N-Oxides / Q000378:metabolism; D006168:Guinea Pigs; D051379:Mice; D009538:Nicotine / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D003497:Cyclic N-Oxides; D009538:Nicotine