Chiral Separation of (R,S)-1,1′-Binaphthyl-2,2′-diyl Hydrogenphosphate by Capillary Electrophoresis Using Monosaccharides as Chiral Selectors

Abstract

Capillary electrophoresis (CE) is a powerful tool for the resolution of enantiomeric compounds owing to its high separation efficiency and its facility to use a wide variety of chiral separation media. [1][2][3][4] In addition to cyclodextrins, which are the cyclic a-1,4-linked oligosaccharides most frequently used as chiral selectors, some linear oligosaccharides have been recently utilized for the separation of optical isomers by CE. [5][6][7][8][9][10][11][12] Kano et al. 10 have reported that the chiral separation of some binaphthol derivatives is achieved by CE with linear a-1,4-linked oligosaccharides such as maltose and maltotriose as chiral selectors. However, no successful resolution of enantiomers by CE with monosaccharides has been achieved so far. In this study, therefore, we attempted the CE resolution of some racemic binaphthyl derivatives (Fig. 1) Boric acid (Kanto Chemical), tris(hydroxymethyl)-aminomethane (Tris) (Nacalai Tesque), tris(hydroxymethyl)methylglycine (Tricine), 2-hydroxy-N-tris-(hydroxymethyl)methyl-3-aminopropanesulfonic acid (TAPSO) and N-cyclohexyl-3-aminopropanesulfonic acid (CAPS) (Dojin, Kumamoto, Japan) were used as buffer components. Monosaccharides were investigated as chiral selectors in capillary electrophoresis of binaphthyl compounds. Among monosaccharides tested, glucose, mannose and their derivatives, except for methyl-b-D-glucopyranoside, were found to be effective for direct separation of racemic mixture of 1,1¢-binaphthyl-2,2¢-diyl hydrogenphosphate (BNP). D-Forms of galactose, sorbose, fructose, ribose, arabinose and xylose failed chiral separation of BNP. We tentatively concluded that monosaccharides (in the case of D-forms) must satisfy the following structural requirements for successful chiral separation of BNP enantiomers: (1) oxygen atom at C-1 is in a-configuration, (2) -OH group at C-4 is downward configurated and (3) the presence of a -CH2OH or -CH3 group at C-5. Thus, in the case of D-glucose, the chiral separation of BNP is anticipated to be achieved predominantly through the hydrogen bonding between oxygen atom at C-1 and hydrogen atom of -OH group at C-4 on D-glucose and hydrogenphosphate moiety of BNP.

Review of aqueous chiral electrokinetic chromatography (EKC) with an emphasis on chiral microemulsion EKC

“…The distribution of Dserine in rat brain was determined. Previous publications that utilized saccharides as chiral selectors demonstrated that a combination of hydrophobic interactions and hydrogen bonding are responsible for chiral recognition [169] with specific requirements for D-glucose chiral selectivity being that the C-1 oxygen is in the a-configuration, the C-4 hydroxyl group is oriented downward, and that either a methyl or hydroxymethyl group be present at C-5 [170].…”

Chiral separation by chromatographic and electromigration techniques. A Review

“…The same author [378] studied the influence of the kind of linkage of different malto-and oligosaccharides on the enantioselectivity. Nakamura et al [379] showed that even monosaccharides such as d-glucose, d-mannose and some of their derivatives can exhibit some limited chiral recognition ability.…”

Chiral capillary electrophoresis: Facts and fiction on the reproducibility of resolution with randomly substituted cyclodextrins

“…The enantiomers were separated with various CDs, e.g., native [16,17] and sulfated CDs [18], heptakis(6-hydroxyethylamino-6-deoxy)-b-CD [19], maleic acid derivative of b-CD [20], CDs in combination with bile salts [21,22], and quaternary ammonium b-CDs in nonaqueous CE [23]. Separation was also performed with noncyclic saccharides, such as mono- [24], di- [25] and polysaccharides [26,27]. As a consequence of the aforementioned findings, the purpose of this study was to investigate the influence of the degree and position of methylation of b-CD on the resolution of BNP enantiomers.…”