Characterization of highly sulfated cyclodextrins

A class of highly sulfated cyclodextrins (HS-CDs) was developed for enantio meric separation of chiral compounds by capillary electrophoresis (CE). The HS-CDs were produced by a facile single-step direct sulfation of cyclodext rin using sulfur trioxide-trimethylamine complex in dimethylformamide. Char acterization of the HS-CDs by electrospray ionization mass spectrometry and by CE using a well-established indirect detection method indicated the spe cies have very narrow heterogeneity in terms of degree of sulfation. Elemen tal analysis of the HS-alpha, beta- and gamma -CDs showed that the average sulfate contents were 11, 12, and 13 per CD molecule, respectively. The C-1 3 NMR of HS-CDs is consistent with the structural assignment of nearly comp lete sulfation at C-6 primary hydroxyl groups and partial sulfation at the C-2 secondary hydroxyls (> 70%), while the C-3 hydroxyls remain unsubstitut ed. Enantiomeric separation by CE using the HS-CDs as chiral selectors show ed that HS-alpha, beta- and gamma -CDs complement each other by exhibiting different chiral selectivities. resulting in resolution of many chiral neut ral, acidic and basic compounds of greatly varying structural features. The part of HS-CD that interacts with the guest molecule during complexation a nd, therefore, the receiving end of the cyclodextrin hydrophobic bucket was surrounded with largely regiospecifically substituted C-2 sulfates and int act C-3 hydroxyls, both at the equatorial positions. Such global regiospeci fic structural arrangement in HS-CDs provides differential diasteroisomeric complexation is proposed to be the principal contributing factor in the re solving racemates. (C) 2001 Elsevier Science B.V. All rights reserved.