Biocatalysis to amino acid-based chiral pharmaceuticals—examples and perspectives

Abstract

The search for and development of new pharmaceutically active structures drives the need for new enantiomerically pure compounds (EPC). Many N-containing structures can be derived beneficially from either l- or d-amino acids [K. Drauz, Chimia 51 (1997) 310–314.]. The largest growth occurs in the area of unnatural amino acids. Two examples discussed from the Degussa portfolio concern (i) d-amino acids [A.S. Bommarius, M. Kottenhahn, H. Klenk, K. Drauz, NATO ASI Series C 381 (1992) 161–174.] as components of LHRH antagonists of which the Degussa's Cetrorelix is a prime example as well as (ii) l- tert-leucine, occurring in a fast-growing number of pharmaceutical compounds under development [A.S. Bommarius, M. Schwarm, K. Stingl, M. Kottenhahn, K. Huthmacher, K. Drauz, Tetrahedron Asymmetry 6 (1995) 2851–2888.]. For d-amino acids, results of the hydantoinase/carbamoylase route will be presented while redox catalysis by way of reductive amination is a suitable process to l- tert-leucine. The number of biocatalytic applications is growing and an updated list is discussed. The presentation will also cover comparisons of biocatalysis with potentially competitive technologies such as enantioselective crystallization, chemical asymmetric synthesis, or chromatographic separation of racemates. Future trends relevant to the perspective for biocatalysis include the need for ever more complex chiral molecules as well as shortened development times in the pharmaceutical industry.