STUDIES ON THE STEREOCHEMISTRY AND STRUCTURE-ACTIVITY RELATIONSHIP OF CHOLINOLYTIC COMPOUNDS 3-(2-PHENYL-2-CYCLOPENTYL-2-HYDROXYL-ETHOXY)-QUINUCLIDINES

Four optical isomers of the new cholinolytic compound 3 - (2 - phenyl - 2 - cyclopentyl - 2 - hydroxyl - ethoxy ) - quinuelidine (Ⅰ) have been asymmetrically synthesized by two methods. Method one: Recemic 1 - phenyl - 1 - cyclopentylepoxy ethane reacting with 3Ror 3S-quinuclidinol produces a mixture of (R-1) and (R-2)or (S-1) and (S-2) respectively. The chemical yields varied from 57% to 78%. The highest % de is 22 and the major product is (R- 1 )or (S- 1 ). Method two: Grignard reaction of 3R or 3S - benzoyl - methoxy - quinuclidine with cyclopentyl magnesium bromide yields a mixture of(R- 1 )and (R- 2 )or (S- 1 )and (S-2). The chemical yield is 80%. The highest % de is 81 and the major product is (R- 2 )or (S-2). Preliminary evaluation of the four new optical isomers revealed the following series of biological potencies: ( R - 2 )>( Ⅰ)>(S - 1)>(R - 1)>(S-2). In the coupling of the compounds with the active centers of M receptors, the absolute Configurations in carbon-3 of the quinuclidinyl group and carbon-2 of the substituted ethyl group play an important role. The influence of carbon-2R is greater than that of carbon-3R on cholinolytic potency.