Molecular Asymmetry and Biological Activity

Easson and Stedman1 have advanced the theory that the differences in biological activity between optical isomers should be considered in exactly the same light as the variations in potency shown by structural isomers. They pointed out that only one optical isomer can come into close contact with the specific receptors, and suggested that the weaker enantiomorph behaves as if one of the active groups is not present at all. In adrenaline, the active groups are : the amino group, the benzene ring with its phenolic hydroxyls, and the alcoholic hydroxyl group. By this view, l-adrenaline can come into complete contact with the receptors, and the weaker enantiomorph, d-adrenaline, cannot. Desoxyadrenaline (epinine) should, therefore, have the same activity as d-adrenaline, except in so far as the activity is modified by changes in physical properties by the presence of the alcoholic hydroxyl group. Easson and Stedman presented evidence that epinine and d-adrenaline do, in fact, have the same effect on blood pressure, and they also found support for the concept in drugs of the miotine type. If the theory is generally true, similar considerations should apply among compounds related to adrenaline : compounds containing a lævo-rotatory B-carbon atom should be the more active, and, with the above reservations regarding physical properties, the activity of the dextro-rotatory enantiomorphs should approximate to that of the desoxy-derivatives.