Resolution and absolute configuration of trans-2-(2,5-dimethoxy-4-methylphenyl)cyclopropylamine, a potent hallucinogen analog

Abstract

An hallucinogen analog, trans-2-(2,5-dimethoxy-4-methylphenyl)cyclopropylamine (DMCPA), was resolved into its 2 enantiomers by fractional crystallization of salts with d- or l-O,O-dibenzoyltartaric acid. A comparison of the ORD [optical rotatory dispersion] and CD [circular dichroism] curves of the N-5-bromosalicylidene derivatives of trans-2-phenylcyclopropylamine of known absolute configuration and of the title compound established the stereochemistry of the latter to be (1R,2S)-(-) and (1S,2R)-(+). It was shown earlier that the (-) isomer shows selective behavioral effects in cats and mice. In the present study it was found that the (-) isomer selectively elicits rabbit hyperthermia when compared with the (+) isomer. In view of the stereoselective ability of the (-) isomer to elicit hallucinogen-like behavioral profiles in these animal models, the proof of absolute configuration lends further support to a new model which interrelates the active binding conformation of phenethylamine hallucinogens to that of serotonin and tryptamines.