Biphasic one-pot synthesis of two useful and separable compounds using nicotinamide cofactor-requiring enzymes: Syntheses of (S)-4-hydroxyhexanoate and its lactone

Several one-pot syntheses of two valuable and separable compounds in a biphasic system using nicotinamide cofactor-requiring enzymes are described. In this system, two synthetic reactions occur in the aqueous phase where the N AD or N ADP cofactor is recycled ≈ 1000 times, and the reduction product is extracted into the organic phase while the oxidation product is retained in the aqueous phase. The effective separation of products and elimination of product inhibition during the reaction makes the biphasic system practical for large-scale synthesis. Several chiral hydroxy compounds of synthetic value have been prepared. Manipulation of N AD-dependent enzymes in synthesis in water-immiscible organic solvent by entrapment of both enzyme and the cofactor in X AD-8 is described.