Studies on the Enantioselective Synthesis of DAB-1
Authors:Hilary Brown, Anasheh Sookezian
Mentor:Donald Deardorff, Carl F. Braun Professor of Chemistry, Occidental College
The stereochemical configuration of an organic compound is often directly linked to its physical and biological properties. Many of the molecules produced by organisms exhibit a specific handedness; consequently the way an organism responds to a molecule depends on its orientation in space. As a result, when designing pharmaceuticals and other targets of biological interest, chemists must keep the issue of chirality in mind. A proposed enantioselective synthesis of the α-glucosidase inhibitor DAB-1 is presented. α-glucosidase enzymes catalyze the metabolism of certain sugars. As an α-glucosidase inhibitor, DAB-1 can help control the body’s glucose level. These α-glucosidase inhibitors have 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 synthetic approach begins with the use of the robust enzyme oxynitrilase, isolated from raw almonds, to induce asymmetry in our achiral starting material, crotonaldehyde. The stereocenter is manipulated and then transposed in a 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. Currently this project is in its later steps of completion. We have successfully synthesized the first eight synthetic intermediates and are now working on finishing the synthetic route.