1 research outputs found
Application of 2D EXSY and qNMR Spectroscopy for Diastereomeric Excess Determination Following Chiral Resolution of βâLactams
Abstract Transâβâlactam isomers have garnered much attention as antiâcancer microtubule targeting agents. Currently available synthetic methods are available for the preparation of enantiopure βâlactams and favour isomeric cis/trans βâlactam mixtures. Indirect chiral resolution offers the opportunity for isolation of exclusively enantiopure transâβâlactams. In this study, liquid chromatography chiral resolution of βâlactams derivatized as diastereomer mixtures with a panel of Nâprotected amino acids is explored, where Nâ(Boc)âLâproline served as the optimal chiral derivatising reagent. Highâperformance liquid chromatography failed to adequately determine diastereomeric excess (de) of resolved diastereomers. Variable temperature, 1Hâ
NMR and 2D EXSY spectroscopic analyses of prolineâderivatised diastereomers were successfully employed to characterise equilibrating rotamers of resolved diastereomers and determine their de. Integration of resolved resonances corresponding to H3 and H4 of the βâlactam ring served as a quantitative qNMR tool for the calculation of de following resolution