Direct high‐performance liquid chromatographic enantioseparation of β‐lactam stereoisomers

Abstract

AbstractHigh‐performance liquid chromatographic methods were developed for the separation of the enantiomers of 12 β‐lactams. Direct separations were performed on chiral stationary phases (CSPs) containing cellulose‐tris‐3,5‐dimethylphenyl carbamate (Chiralcel OD‐RH and OD‐H columns), the macrocyclic glycopeptide antibiotic teicoplanin (Chirobiotic T column), or teicoplanin aglycone (Chirobiotic TAG column) as the chiral selector. It was clearly established that, with teicoplanin‐based columns, the teicoplanin aglycone was most often responsible for the enantioseparation of the β‐lactams. The difference in enantioselective free energy between the aglycone CSP and the teicoplanin CSP was in the range between 0.02 and 0.97 kJ mol−1 for these β‐lactam stereoisomer separations. The separations were carried out with high selectivity and resolution, and the method was therefore suitable for monitoring of the enantiomeric excess after chiral synthesis. The Chirobiotic and Chiralcel columns appear to be highly complementary to one another. The best separation of this class of β‐lactam compound could be obtained using the Chirobiotic TAG in the polar‐organic mode plus the Chiralcel OD‐H in the normal‐phase mode. The elution sequence was also determined. Chirality 17:193–200, 2005. © 2005 Wiley‐Liss, Inc.