The relation between biological activity and the degree of resolution of optical isomers

Abstract

Abstract Previous reports of the low stereospecificity of benzhexol can be ascribed to inadequate resolution of the samples tested and a report of much higher stereospecificity has been confirmed. The two enantiomers have been found to differ over 1000-fold in their affinity for the postganglionic acetylcholine receptors of the guinea-pig ileum. Mixtures of the enantiomeric forms of phenylcyclohexyl-glycolloylcholine and of benzhexol have been tested on this preparation and the dose-ratios used to calculate apparent affinity constants. With both pairs the results indicate that the two enantiomers compete with the agonist and with each other and justify the use of the stereo-specific index to set limits to the degree of resolution. For compounds such as these, in which one enantiomer has appreciably higher biological activity than the other, this biological method for assessing stereochemical purity is likely to be at least as satisfactory as any nuclear magnetic resonance method currently in use, because of the very great sensitivity of the stereospecific index to the degree of resolution.