A Family of Single-Isomer Chiral Resolving Agents for Capillary Electrophoresis. 1. Heptakis(2,3-diacetyl-6-sulfato)-β-cyclodextrin

Abstract

A new, moderately hydrophobic, single-isomer charged cyclodextrin, the sodium salt of heptakis(2,3-diacetyl-6sulfato)--cyclodextrin, has been synthesized and used to separate a variety of neutral, weak acid, strong base, weak base, and zwitterionic racemic enantiomers in low-pH and high-pH background electrolytes. Separation selectivity for the netural analytes rapidly decreases as the concentration of heptakis(2,3-diacetyl-6-sulfato)--cyclodextrin increases. For charged analytes, selectivity can increase, decrease, or pass a maximum, depending on the numeric values of the respective complexation constants and ionic mobilities. In addition to separation selectivity, the extent of peak resolution that can be realized strongly depends on the magnitude of the dimensionless electroosmotic flow. Heptakis(2,3-diacetyl-6-sulfato)--cyclodextrin proved to be a broadly applicable chiral resolving agent.

Chiral separation by chromatographic and electromigration techniques. A Review

“…A series of single isomer b-and g-CD derivatives was introduced by Vigh's group [351][352][353][354]. These authors prepared derivatives completely sulfated in 6-position and completely substituted on their larger rims with hydrophylic groups, moderately hydrophobic groups or hydrophobic methyl functional groups.…”

Single‐isomer sulfated α‐cyclodextrins for capillary electrophoresis: Hexakis(2,3‐di‐O‐methyl‐6‐O‐sulfo)‐α‐cyclodextrin, synthesis, analytical characterization, and initial screening tests

“…Next, dry NaH (1.2-fold molar excess with respect to the OH groups in (1)) was added to the flask under a dry nitrogen gas atmosphere. Intermediate (2) was dissolved in dry THF, mixed with CH 3 I (1.35-fold molar excess with respect to the OH groups in (1)), and added drop-wise to the stirred NaH suspension in the flask at a rate that maintained about 307C in the flask to obtain intermediate (3), hexakis(2,3-di-O-methyl-6-dimethyl-t-butylsilyl)-a-CD. Intermediate (3) was purified by fractional crystallization and analyzed by nonaqueous reversed-phase HPLC using a 250 mm64.6 mm ID column packed with 5 mm Luna C-18 silica (Phenomenex, Torrence, CA, USA), and a 2 mL/min isocratic mobile phase of ethylacetate:methanol (35:65).…”

“…99%. The structure of intermediate (3) was confirmed by high-resolution MALDI-TOF-MS [12] using a Voyager Elite XL mass spectrometer equipped with delayed extraction capability (Perceptive Biosystems, Framingham, MA, USA), and 1 H NMR, 13 C NMR, double-quantum filtered 1 H-1 H correlation spectroscopy (COSY) and 1 H- 13 C heteronuclear correlation spectroscopy (HETCOR) using Varian UnityPlus spectrometers (300 MHz and 500 MHz, both from Varian, Walnut Creek, CA, USA). Hexakis(2,3-di-O-methyl-6-dimethyl-t-butylsilyl)-a-CD was then converted into intermediate (4), hexakis(2,3-di-O-methyl)-a-CD, by removing the dimethyl-t-butylsilyl protecting group with hydrogen fluoride (HF) in ethanol.…”

“…That review pointed out that sulfated cyclodextrins [2], including the single-isomer, regioselectively substituted 6-O-sulfo CDs [3][4][5][6][7][8][9][10] were the most widely used resolving agents for the separation of the enantiomers of pharmaceuticals. The objective of this paper is to describe the large-scale synthesis, analytical characterization and initial CE screening results for the third member of the single-isomer, sulfated a-CD family, the sodium salt of hexakis(2,3-di-O-methyl-6-O-sulfo)-a-CD (HxDMS) that completes the array of single-isomer, 6-O-sulfo CDs now available, namely the three b-CD derivatives (heptakis(6-Osulfo)-b-CD, HS [4], heptakis(2,3-di-O-acetyl-6-O-sulfo)-b-CD, HDAS [3], and heptakis(2,3-di-O-methyl-6-Osulfo)-b-CD, HDMS [5]), the three g-CD derivatives (octakis(6-O-sulfo)-g-CD, OS [7], octakis(2,3-di-O-acetyl-6-Osulfo)-g-CD, ODAS [6], and octakis(2,3-di-O-methyl-6-Osulfo)-g-CD, ODMS [8]), and the two a-CD derivatives (hexakis(6-O-sulfo)-a-CD, HxS [10], and hexakis(2,3-di-O-acetyl-6-O-sulfo)-a-CD, HxDAS [9]).…”

Potential of flow‐counterbalanced capillary electrophoresis for analytical and micropreparative separations

“…rations by the same group [12]. The authors used the carrier ability of a charged chiral selector as opposite mobility to the migration of chiral analyte.…”