Biocatalytic Formation of C-C Bonds

Key words

enzymes - kinetic resolution - aerobic oxidative C-C coupling - C-H activation

Significance

The biocatalytic formation of C-C bonds by means of a kinetic resolution of reticuline derivatives is reported. The involved biocatalytic system consists of an aerobic berberine bridge enzyme (BBE) from Eschscholzia califor­nica. Additionally, catalase was incorporated to degrade hydrogen peroxide, which proved to inhibit the enzyme activity at elevated concentrations. The BBE exhibited high tolerance towards virtually any organic solvent and even showed full activity in mixtures of water and toluene. The re­gioselectivity of the C-H activation triggered ring closure represented only a minor problem; the concentrations of the OH group isomeric scoulerine-type products were below 10% in all cases.

Comment

Biocatalysis is a growing field in organic synthesis since many chemical transfor­mation can be catalyzed by enzymes. Furthermore, activity and selectivity are often superior to purely chemical methods. In the present report, C-C couplings are catalyzed under entirely environmentally benign conditions. The remarkable fact that the enzyme successfully operates in the presence of high concentrations of organic solvents, shows its high potential for further synthetic applications. However, the bottleneck of the procedure is the high specifity since only few substrates were successfully transformed. A solution to this problem could be provided by directed evolution (see Review below). Further research along these lines involving the powerful class of berberine bridge enzymes (BBE) can be anticipated.

Review: M. T. Reetz Angew. Chem. Int. Ed. 2011, 50, 138-174.