Effects of caffeine on stereoselectivities of high cell density biotransformations of cyclic β-keto esters with Saccharomyces cerevisiae

Caffeine affects the stereoselectivity of microbial high cell density reductions with commercial grade Saccharomyces cerevisiae ( Baker's yeast). Cyclic beta-keto esters ethyl 2-oxocyclopentanoate ( 1) and ethyl 2-oxocyclohexanoate ( 3) were shown to be reduced with increased diastereoselectivity(1:90.1 -> 92.1% de, 3: 75.0 -> 90.0% de) after addition of caffeine. Effects on enantioselectivity were less pronounced ( 1: 97.3 -> 98.5% ee, 3: 90.1 -> 92.1% ee). The observations are ascribed to the action of caffeine on cellular calcium homeostasis. These effects are accompanied by caffeine-induced cell-death, which preferably takes effect on pre-stressed cells which were found to decrease diastereoselectivity.