Sitagliptin Enzymatic Synthesis of Chiral Amine

The chemical synthesis of sitagliptin [25,26] involved an as5mmetric hydrogenation of an enamine at high pressure using a rhodium-based chiral catalyst [27]. The chemical process suffers from inadequate stereoselectivity and a product stream contaminated with rhodium, necessitating additional purification steps at the expense of yield to upgrade both enantiomeric excess and chemical purity. 

To develop a biocatalytic process, screening of commercially available transaminases by Merck and Codexis provided no enz3une with detectable activity for amination of tile prositagliptin ketone 6 [28]. They therefore applied a combination of in silico design and directed evolution in an effort to confer such an enzyme. 

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