Application of enzymes in Organic Chemistry

Application of enzymes in Organic Chemistry

Since the very beginning enzymes are an essential tool in organic chemistry. Although occasionally not at centre stage of chemistry their application dates back to Liebigs and Wöhlers application of Hydroxynitrile lyases 180 years ago, Emil Fischers application of enzymes in sugar chemistry, when he formulated the lock and key hypothesis and to the first enantioselective synthesis ever described (L. Rosenthaler, Biochem. Z., 1908, 14, 238-253; Scheme 1). Here again Hydroxynitrile lyases are the enzymes of choice. Indeed these enzymes are still in use in our group. Both, the immobilisation (Chem. Soc. Rev., 2013, 42, 6308 - 6321) and application in organic solvents (Chem. Eur. J. 2010, 16, 7596 – 7604), as well as new Hydroxynitrile lyases (FEBS Journal 2013, 280, 5815–5828) or their genetic modification are studied. In this way these versatile tools are modernised continuously; often in collaboration with other groups.

Scheme 1: First enantioselective reaction in chemistry. The topic is still under investigation in Delft and countless variations and additions are done.

The range of enzymes was extended since 1908 and today we study other C-C bond forming enzymes and many hydrolytic and redox enzymes.

  • Trans ketolase (Top. Catal. 2013, 56, 750–764) for the environmentally benign C-C bond synthesis starting from sugars.
  • Alcohol dehydrogenases for the enantioselective synthesis of alcohols and for ketone synthesis (see also redox enzymes)
  • Enoate reductases for the synthesis of enantiopure building blocks (see also redox enzymes)
  • Hydratases for the enantioselective addition of water to C=C bonds. Chemically this reaction is extremely difficult due to the poor nucleophilicity of water (Scheme 2)
  • Nitrile reductase, an enzyme that can reduce nitriles under mild condition (Scheme 3)

Scheme 2: Chemically the addition of water to isolated C=C and in Michael fashion is a question almost unanswered. By applying enzymes these conversions can be performed under mild conditions with high selectivity (Chem. Commun. 2011, 47, 2502–2510. and Eur. J. Org. Chem. DOI: 10.1002/ejoc.201301230).

Scheme 3: Nitrile reductase is a new class of enzymes only described recently. The scope of the E. coli enzyme is currently studied in Delft (Enz. Microb. Tech. 2013, 52, 129– 133).

For further details please contact:  u.hanefeld@remove-this.tudelft.nl or f.hollmann@remove-this.tudelft.nl

 

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