Molecular Pharmacology, Vol 19, 517-519, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

On the Stereochemistry of Dopaminergic Ergoline Derivatives

¹ Biochemistry Department, University of Toronto, Toronto, Ontario, Canada M5S 1A8, and Departments of Medicine (Neurology) and Pharmacology, University of Washington, Seattle, Washington 98195

Three-dimensional structures of bromocriptine hydrochloride, bromocriptine free base, and apomorphine hydrochloride are compared in order to delineate those portions of the molecules responsible for dopaminergic activity. It is shown that the orientation of the nitrogen atom lone pair electrons in the ergoline derivatives is not necessarily fixed by the configuration at the asymmetrical carbon atom, and it is suggested that stereochemical comparisons should be based primarily on superpositions of electronegative moieties, rather than aromatic nuclei.

Note:
ACKNOWLEDGMENT We thank Dr. H. P. Weber for the unpublished structural data for bromocriptine free base.