A Retrosynthesis Approach for Biocatalysis in Organic Synthesis

5 years ago

A Retrosynthesis Approach for Biocatalysis in Organic Synthesis

Uwe T. Bornscheuer, Leandro S. M. Miranda, Rodrigo O. M. A. de Souza

For the planning of an organic synthesis route, the disconnection approach guided by retrosynthetic analysis of possible intermediates and the chemical reactions involved, back to ready available starting materials, is well established. In contrast, such concepts just get developed for biocatalytic routes. In this Review we highlight functional group interconversions catalyzed by enzymes. The article is organized rather by chemical bonds formed—exemplified for C−N, C−O- and C−C-bonds—and not by enzyme classes, covering a broad range of reactions to incorporate the desired functionality in the target molecule. Furthermore, the successful use of biocatalysts, also in combination with chemical steps, is exemplified for the synthesis of various drugs and advanced pharmaceutical intermediates such as Crispine A, Sitagliptin and Atorvastatin. This Review also provides some basic guidelines to choose the most appropriate enzyme for a targeted reaction keeping in mind aspects like commercial availability, cofactor-requirement, solvent tolerance, use of isolated enzymes or whole cell recombinant microorganisms aiming to assist organic chemists in the use of enzymes for synthetic applications. Biocatalysis: This Review highlights retrosynthesis concepts using enzymes as biocatalysts exemplified for C−N, C−O and C−C bond formations. Furthermore, a range of examples for the combination of biocatalysis with chemical reactions is illustrated for the synthesis of drugs and APIs such as Crispine A, Sitagliptin or Atorvastatin. Basic guidelines are provided as to how to choose the most appropiate enzyme for a targeted reaction.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201702235