A novel, single-isomer, sulfated cyclodextrin for use as a chiral resolving agent in capillary electrophoresis: the sodium salt of octakis(2,3-di-O-methyl-6-O-sulfo)-γ-cyclodextrin

Abstract

A novel, single-isomer, sulfated cyclodextrin, the sodium salt of octakis(2,3-di-O-methyl-6-O-sulfo)cyclomaltooctaose (ODMS) was used as a chiral resolving agent in both aqueous and non-aqueous chiral mediated electrophoretic separation of a large set of pharmaceutically active weak acids and bases as well as UV absorbing neutral enantiomers. Eight of the thirteen weak acids and 45 of the 48 weak bases showed selectivity sufficient for baseline resolution in one or more of the three background electrolytes (BGE's) used. Seven of the sixteen neutral compounds screened were found to exhibit selectivity in at least one of two aqueous BGE's. A four step synthetic method was used to produce on a large scale the title compound in greater than 98% purity. Synthetic intermediates and the final product were characterized according to purity by HPLC-ELSD and indirect UV-detection capillary electrophoresis (CE), respectively. X-ray crystallography, MALDI-TOF mass spectrometry and ¹H as well as ¹³C NMR spectroscopy allowed for unambiguous characterization of the structure of each intermediate and the final product.