Enantioselective bioconversion of ketones and alcohols in organic solvents with immobilized yeast cells

The importance of chiral compounds and the methods used to manufacture and purify them is increasingly important for the pharmaceutical and specialty chemical industries. However, the chemical synthesis of molecules with chiral centers often results in a racemic mixture of isomers. An attractive alternative is to employ catalysts derived from biological sources. Biocatalysts, such as enzymes and whole cells, have demonstrated the ability to stereoselectively catalyze a number of reactions. This dissertation is concerned with investigating the use of whole cells for the production of chiral molecules in organic solvents. A novel strain of the yeast Saccharomyces cerevisiae, which was found to possess higher catalytic activity than previously studied yeast, was utilized. The yeast cells were immobilized by entrapment within calcium alginate beads and were found to possess the ability to stereoselectively reduce prochiral ketones and oxidize chiral alcohols to equilibrium conversion in organic solvents. The yeast were also used to resolve racemic mixtures of alcohols by selectively converting one enantiomer to the corresponding ketone, while leaving the other unchanged. Evaluation of the internal diffusional limitations for reduction and oxidation reactions revealed that internal diffusional limitations are negligible for the reaction systems proposed. It was found that the observed initial rates of the reactions studied varied inversely with reactant partitioning between the organic solvent and alginate beads. A kinetic model was developed to describe the initial reaction rate of hexanone reduction. By expressing the rate as a function of substrate concentration within the alginate beads, it is possible to predict the initial reaction rate in different solvents.