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The
Enantioselective Synthesis of DAB-1 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. Support provided by: Occidental Research Award to Prof. Deardorff and Howard Hughes Medical Institute Undergraduate Science Education Grant |
