Unnatural congeners

Belhna, F., Anselmi, C., and Rossi, R. (2002) Total synthesis of ruhrolide M and some of its unnatural congeners. Tetrahedron Lett., 43, 2023-2027. 

Nomicotine, in which the N-methyl is replaced by hydrogen, is somewhat less potent and active than nicotine in most assays (102). R- and S-nomicotine are equipotent with R-(+)-nicotine,the less active, unnatural enantiomer, in a rat brain membrane-binding assay (103). In that study, S-(-)-nicotinewas 13 times more potent than its R- enantiomer. Replacement of the N-methyl of nicotine with ethyl or n-propyl eauses an exponential loss of peripheral nicotinic effect (102). Anabasine (51), a relatively minor alkaloidal constituent of tobacco, demonstrated approximately 1/10 the affinity of nicotine in a binding assay (104). A synthetic azetidine congener (52) of nicotine binds with the same affinity as nicotine to rat brain membrane tissue, and it displayed a greater potency than nicotine in a rat behavioral assay (105). Evaluation of a series of 6-substituted nicotine derivatives (53) led to the conclusion that affinity for rat brain... 

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