Active pharmaceutical epimerization

The product mandate for this project required that the active pharmaceutical ingredient (API) needed to be a single isomer. Methodology reported in the literature, for the general class of which cefovecin is a member, provided an epimeric diastereoisomer mixture of 3 (which became cefovecin sodium) and 4 (UK-287076 sodium). Both compounds are potent, but the (S) absolute configuration at the tetrahydrofuran (THF) C-2 center was selected for commercial development (Figure 11.1). 

More detailed studies of epimerization in the azepanone series indicated that these compounds were configurationally stable over a pharmaceutically relevant time-scale [19]. Structure-activity relationships developed in previous series were applied successfully to the azepanone scaffold, yielding extremely potent enzyme inhibitors that exhibited good diastereomeric selectivity as well as reasonable selectivity versus cathepsin K homologues. 

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