Chiral ion-pair chromatography on porous graphitized carbon using N-blocked dipeptides as counter ions

Two newly synthesized chiral di-anionic counter ions were tested for enanti omeric resolution of a set of amino alcohols on porous graphitized carbon, Hypercarb. Z-L-Aspartyl-L-proline dissolved in methanol baseline resolved n ine of 12 tested racemates. One of its diastereoisomers, Z-L-aspartyl-D-pro line was also tested but resulted in low separation factors, <1.1. Sodium h ydroxide was added to the mobile phase in order to titrate the counter ion to its mono- or di-anionic form. Results show that the di-anionic form was found to be superior to the mono-anionic form regarding enantioselectivity. Increased content of the counter ion in the mobile phase, with constant ra tio between counter ion and sodium hydroxide concentration, decreased reten tion but only slightly affected enantioselectivity. Increased retention and enantioselectivity were observed with decreased column temperature. Resolu tion factors >3 were obtained between the enantiomers in atenolol and metop rolol with a total retention time of less than 15 min. Further, all four st ereoisomers of an analogue to metoprolol were separated using Hypercarb and a mobile phase of 5 mM Z-L-aspartyl-L-proline and 9 mM sodium hydroxide in methanol. (C) 2001 Elsevier Science B.V. All rights reserved.