This contribution describes the development of a ketoreductase enzyme over four rounds of directed evolution and the associated process development that enabled a practical, scalable process to (S)-licarbazepine (eslicarbazepine).

The enantioselective synthesis of C-C bonds is often the pivotal step of a synthesis. Nature has made a variety of versatile enzymes available that catalyse this type of reaction very selectively under mild conditions. Cyanohydrins, acyloins (alpha-hydroxy ketones), alpha-hydroxy acids and aldols (beta-hydroxy ketones) are very efficiently synthesised enantioselectively with the aid of C-C bond forming enzymes, which we discuss in this tutorial review. In the case of the alpha-hydroxy acids the applications of nitrilases in a synthetic dkr even allows a disconnection that has no enantioselective chemical equivalent.

Organic chemistry Z 0200Enantioselective C-C Bond Synthesis Catalyzed by Enzymes -[42 refs.]. -(SUKUMARAN, J.; HANEFELD*, U.; Chem. Soc. Rev. 34 (2005) 6, 530-542; Gebouw Scheikd., Tech. Univ. Delft, NL-2628 BL Delft, Neth.; Eng.) -Lindner 39-240

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(À)-Deoxynupharidine has been synthesised via an intermediate that can also be used for other Nuphar alkaloids. Significants teps include the optimisede nzymatic resolution of an allenic alcohol, highly diastereoselective silvercatalysed cyclisation of an allenic hydroxylamine, selective cross-metathesis,d iastereoselectivei ntramolecular reductive amination,a nd stereoelectronically controlled enolate alkylation.