An Enantioselective Synthesis of DAB-1

Abstract

A synthetic route for enantio-pure α-glucosidase inhibitor DAB-1 is investigated. In the mammalian digestive tract, the enzyme α-glucosidase catalyzes a key step in the degradation of glycogen. By inhibiting this enzyme, the rate at which glucose is produced in the cell can be specifically controlled. The control of blood glucose levels has far reaching use in the treatment of diabetes and also hypoglycemia. The enatiomeric pair of 1,4-dideoxy-1,4-imino-arabinitol (DAB-1 and LAB-1) has shown to be prominent inhibitors of α-glucosidases. Derivatives of DAB-1 have also been used to disrupt the construction of HIV virus glycoproteins within host cells. It is for these reasons that efficient, economical syntheses of DAB-1 and LAB-1 have wide importance to the scientific community. Using a robust enzyme named oxynitrilase, derived from almonds, we establish chirality in an achiral molecular backbone and maintain enantiomeric integrity throughout subsequent synthetic steps in enatiomeric excesses of >95%. By utilizing Palladium(0) catalysis, we can transpose the stereocenter while maintaining enantiomeric integrity throughout the synthetic route. Further manipulation of the chiral backbone affords the title compound in an efficient and economical manner.