Title

The Enantioselective Synthesis of DAB-1 Meghan Whalen and Kevin Grier-Roddy

Document Type

Article

Publication Date

2010

Abstract

An enantioselective synthetic route for the a-glucosidase inhibitor DAB-1 is presented. This enantiopure product has potential applications in the research related to treatments for diabetes, cancer, genetic disorders, and lysosomal storage diseases. Derivatives of DAB-1 have also been used to disrupt the production of HIV virus glycoproteins within host cells. These applications arise from DAB-1?s ability to interfere with the activity of the enzyme a-glucosidase as related to the digestion of sugars present in the bloodstream. Our novel synthetic approach utilizes a naturally occurring protein, oxynitrilase, found in defatted almonds (a cheap and readily available reagent) in order to reliably induce asymmetry in our achiral starting material, crotonaldehyde. This induced chiral center is then transposed via the Palladium-catalyzed 1,3 chiral shift (5), as prepared for via the addition of the stereoisomer-maintaining ester group. The palladium-catalyzed 1,3 chiral shift additionally allows for the addition of nitrogen (important both biologically and in the direct context of our synthesis), while maintaining enantiopure product. Further manipulation of the chiral backbone affords the title compound, DAB-1. Thus far our results have been successfully characterized with NMR and GC analysis.

Advisor

Don Deardorff

Department

chem

Support

Occidental ResearchAward to Prof. Deardorff and Howard Hughes Medical Institute Undergraduate Science Education Grant

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