Synthesis of Heptakis-2-O-Sulfo-Cyclomaltoheptaose, a Single-Isomer Chiral Resolving Agent for Enantiomer Separations in Capillary Electrophoresis

Single-isomer sulfated cyclodextrins (SISCDs) have proven to be reliable,\neffective, robust means for separation of enantiomers by capillary electrophoresis (CE).\nSISCD derivatives used as chiral resolving agents in CE can carry the sulfo groups either\nat the C2, C3 or C6 positions of the glucopyranose subunits which provides varied\nintermolecular interactions to bring about favorable enantioselectivities.\nThe first single-isomer, sulfated β-CD that carries the sulfo group at the C2\nposition, the sodium salt of heptakis(2-O-sulfo-3-O-methyl-6-Oacetyl)\ncyclomaltoheptaose (HAMS) has been synthesized. The purity of each synthetic\nintermediate and of the final product was determined by HILIC and reversed phase\nHPLC. The structural identity of each intermediate and the final product was verified by\n1D, and 2D NMR, and MALDI-TOF mass spectrometry.\nHAMS has been used as chiral resolving agent for the CE separation of a set of\nnonionic, weak base and strong acid enantiomers in pH 2.5 background electrolytes.\nRapid separations with satisfactory peak resolution values were obtained for the enantiomers of most of the nonionic and weak base analytes. Typically, low\nconcentrations of HAMS were required to effect good enantiomer resolution.\nThe trends in the effective mobilities and separation selectivities as a function of\nHAMS concentrations followed the predictions of the ionic strength-corrected charged\nresolving agent migration model (CHARM model). HAMS showed poor complexation\nwith the anionic strong electrolyte enantiomers for which no peak resolution was\nobserved. The separation patterns observed with HAMS as chiral resolving agent were\ncompared with those of other β-cyclodextrin analogues, including heptakis(2-O-methyl-\n3-O-acetyl-6-O-sulfo)-b-cyclodextrin (HMAS), heptakis(2-O-methyl-3,6-di-O-sulfo)-b-\ncyclodextrin (HMdiSu), heptakis(2,3-di-O-acetyl-6-O-sulfo)-b-cyclodextrin (HDAS)\nand heptakis(2,3-di-O-methyl-6-O-sulfo)-b-cyclodextrin (HDMS).