Preparation of Positive Inotropes Using Glycidyl Derivatives: Influence of Metal Ions and Solvent on Stereochemical Outcome.

Abstract The choice of base and solvent has a dramatic effect on the attack of nitrogen nucleophiles on enantiomerically enriched glycidyl sulfonates 8. Under the proper conditions attack can be largely limited to displacement of the sulfonate moiety thus retaining the original stereochemistry. Conditions were also noted where the initial attack resulted from epoxide opening. Subsequent attack of the intermediate alkoxide on the sulfonate group then yielded a product of opposite stereochemistry. The methodology was applied to the syntheses of both enantiomers of a new selective, positive ionotropic agent, 1 (carsatrin), 4-[bis(4-fluorophenyl)methyl]-(α-[9H-purin-6-ylthio)methyl]-1-piperazineethanol.