ABSTRACT
Chromatographic resolution of enantiomers has become the accepted method for generation of active pharmaceutical intermediates (APIs) in early phase development. Continuous processes such as simulated moving bed (SMB) are recognized as alternative approaches for manufacturing of larger quantities of enantiomerically pure compounds. Steady state recycle (SSR) technology was initially described in 1998 [C.M. Grill, L. Miller, J. Chromatogr. A 827 (1998) 359] and has recently become a common technique in some laboratories. Batch chromatography, SSR, and SMB processes should be considered "phase appropriate" technologies. Phase appropriate technology refers to the scale of separation required in a step of the drug development process. SSR is phase appropriate technology for producing 100 g to several kilogram quantities of material. In this report, we will describe development and scale up of chiral separations utilizing the SSR technique for six different APIs utilizing several different chiral stationary phases and compare the efficiencies of both SSR and batch chromatographic techniques.
Subject(s)
Chromatography, Liquid/methods , Pharmaceutical Preparations/isolation & purification , Pharmaceutical Preparations/chemistry , Spectrophotometry, UltravioletABSTRACT
Cdc25A assay-guided fractionation of a fermentation broth derived from a Streptomyces sp. resulted in the isolation of four novel naphthoquinones 1-4. Structures of these compounds were deduced by NMR and mass spectrometry. Two of them, 3 and 4, incorporate a modified cysteine residue which is observed for the first time in this class of natural products. Naphthoquinones 1-4 showed weak activity against cdc25A phosphatase.
