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

The hallucinogen analogue DMCPA was separated into its two mirror-image forms using a crystallization technique. By comparing the optical properties of these forms to a related compound of known structure, the absolute configuration of the (-) isomer was determined to be (1R,2S) and the (+) isomer (1S,2R). Earlier work showed the (-) isomer causes selective behavioral effects in cats and mice; this study found it also selectively raises body temperature in rabbits compared to the (+) isomer. This stereoselective activity supports a model linking the active binding conformation of phenethylamine hallucinogens to that of serotonin and tryptamines.

Study at a glance

Abstract

An hallucinogen analogue, trans-2-(2,5-dimethoxy-4-methylphenyl)cyclopropylamine (DMCPA), was resolved into ints two enantiomers by fractional crystallization of salts with d- or l-O,O-dibenzoyltartaric acid. A comparison of the ORD and CD 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)-(+). We have earlier shown that the (-) isomer shows selective behavioral effects in cats and mice. In 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.