Nichols D E, Woodard R, Hathaway B A, Lowy M T, Yom K W
J Med Chem. 1979 Apr;22(4):458-60. doi: 10.1021/jm00190a021.
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.
一种致幻剂类似物，反式-2-(2,5-二甲氧基-4-甲基苯基)环丙胺(DMCPA)，通过与d-或l-O,O-二苯甲酰酒石酸形成盐进行分步结晶，拆分成其两种对映体。对已知绝对构型的反式-2-苯基环丙胺的N-5-溴水杨醛衍生物和标题化合物的ORD和CD曲线进行比较，确定后者的立体化学为(1R,2S)-(-)和(1S,2R)-(+)。我们之前已经表明，(-)异构体在猫和小鼠中表现出选择性行为效应。在本研究中发现，与(+)异构体相比，(-)异构体选择性地引起兔体温过高。鉴于(-)异构体在这些动物模型中引发类似致幻剂行为特征的立体选择性能力，绝对构型的证明进一步支持了一个新模型，该模型将苯乙胺致幻剂的活性结合、构象与血清素和色胺的构象联系起来。
