Isolating Enantiopure a,b-Unsaturated Cyanohydrins by Exposing the Achiral Analog Substrates to Oxynitrilase. Jason M. Chapman, Anna Nelson & Aaron Pace

Abstract

Medicinal applications of single-enantiomer drugs (SED's), or pharmaceutical drugs with considerably reduced side effects, are at the forefront of our research efforts. Because separating one enantiomer from another is inefficient and very difficult, the manufacturing of SED?s will rely mainly on synthetic pathways that isolate or 'prefer' one enantiomer over the other. With the aid of Nature's abundant source of oxynitrilase, an enzyme found in raw almonds, our research group has realized great success in a synthetic scheme that isolates single enantiomers. Five different a,b-unsaturated aldehydes were reacted with HCN and oxynitrilase, and four of those reactions were observed to yield the (R)-cyanohydrin with an enantiomeric excess greater than 99%. 400 MHz ¹HNMR Spectroscopy was used to determine this excess by comparing the integration data from the enantiocontrolled reaction to that of the racemic (R/S) reaction. The racemic mixture was created when the reaction took place without the presence of oxynitrilase. Subsequent reactions (i.e. carbonates, imidates, etc.) also revealed that the enantiopure configuration of the stereocenter was preserved, thus strengthening the viability of this novel methodology as a means for developing chiral frameworks for SED's. Future plans include testing oxynitrilase's enantioselective tolerance by exposing more achiral substrates to the enzyme, to create a broader base of potential SED building blocks.