Studies on the Enantioselective Synthesis of DAB-1
Authors:Hilary Brown, Anasheh Sookezian
Mentor:Donald Deardorff, Carl F. Braun Professor of Chemistry, Occidental College
A proposed enantioselective synthesis of the α-glucosidase inhibitor DAB-1 is presented. The enzyme, α-glucosidase, interferes with the metabolism of certain sugars. As an α-glucosidase inhibitor, DAB-1 can help control the body’s glucose level. It has the potential to be used in the treatment of diabetes and hypoglycemia. In addition, derivatives of DAB-1 have been used to interfere with the production of HIV glycoproteins within host cells. Our unique, highly versatile synthetic approach begins with the use of the robust enzyme, oxynitrilase, isolated from defatted, raw almonds, to induce asymmetry with >99% enantiomeric excess in our achiral starting material, crotonaldehyde. The stereocenter is then transposed in the palladium-catalyzed 1,3-chiral shift. This is a crucial step in our synthetic route that introduces the necessary functionality while maintaining enantiomeric integrity. Further manipulation of the carbon backbone is expected to afford the title compound.