Savile, Janey, Mundorff, Moore, Tam, Jarvis, Colbeck, Krebber, Fleitz, Brands, Devine, Huisman, and Hughes. Biocatalytic Asymmetric Synthesis of Chiral Amines from Ketones Applied to Sitagliptin Manufacture. Science, 2010, 329, 305-309. DOI: 10.1126/science.1188934.
Here’s a short follow-up on this previous post, which covered a biocatalytic reaction developed by Codexis to make the key intermediate in the synthesis of Merck’s drug montelukast (aka Singulair). The 2010 Presidential Green Chemistry Awards were just announced, and the award for “Greener Reaction Conditions” went to Merck and Codexis for developing an enantioselective biocatalyst for the synthesis of sitagliptin, Merck’s blockbuster anti-diabetes drug (aka Januvia). This work is also the subject of a recently-published Science paper from Merck and Codexis.
The paper describes the development of an enzyme-catalyzed replacement for the final reaction in the synthesis of sitagliptin, in which a ketone functionality is converted into an amine. Continue reading