Studies on phenethylamine hallucinogens. 2. Conformations of arylmethoxyl groups using 13C NMR.
Carbon-13 chemical shift (delta) and spin-lattice relaxation time (T1) measurements were used to determine the conformation around the Ar-OCH3 bond of the arylmethoxyl groups in a series of substituted phenethylamines. Methoxyl groups flanked by two ortho substituents have delta 13C values higher (60.5-62.5 ppm) than those with one or no ortho substituents ((55.5-57.5 ppm) and T1 values considerably longer than those of the other methoxyl groups in the same molecule. These measurements indicate that methoxyl groups with two ortho substituents acquire the out-of-plane conformation, while those with one or no ortho substitutents exist in the planar conformation. Phenethylamine analogues with methoxyl groups in the out-of-plane conformation have low or no psychotomimetic activity. A possible explanation is that the out-of-plane methoxyl group interferes with the binding of the electron-rich methoxy-substituted aromatic ring to a corresponding electron-deficient component on the active site of the receptor.
D006213:Hallucinogens / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010627:Phenethylamines / Q000032:analysis*; D013329:Structure-Activity Relationship
D006213:Hallucinogens; D010627:Phenethylamines