Bis-[6-oxa-(2-carboxylbenzenesulfonyl-butanedioic acid 1,4 monoester-4)-beta-cyclodextrin, preparation method and application thereof

Abstract

The invention relates to bis-[6-oxa-(2-carboxylbenzenesulfonyl-butanedioic acid 1,4 monoester-4)-beta-cyclodextrin, a preparation method and application thereof as chiral selective agent in high performance capillary electrophoresis (HPCE), namely being prepared into a chiral electrophoresis column and a mobile phase chiral additive for detachment of chiral substances. The molecular formula of the bis-[6-oxa-(2-carboxylbenzenesulfonyl-butanedioic acid 1,4 monoester-4)-beta-cyclodextrin is determined to be C64H84O49S2; beta-CD-B2 is used as the HPCE mobile phase chiral additive to separate chiral substances of phenylglycinol, anisodamine, isoprenaline and propafenone to realize baseline separation; beta-CD-B2 is used for preparing a chiral HPCE column to separate chlortrimeton, bupivacaine, procaine, atenolol, anisodamine, propafenone, lobeline and other chiral substances to realize the baseline separation. Therefore, a novel HPCE quantitative measurement method for a single enantiomerof various chiral substances can be established.

Description

technical field [0001] The present invention relates to bis-[6-oxo-(2-m-carboxybenzenesulfonyl-succinic acid 1,4 monoester-4)]-β-cyclodextrin and its preparation method and as a chiral selective agent in high-efficiency capillary electrophoresis (HPCE) applications, that is, the preparation of chiral HPCE electrophoresis columns and mobile phase chiral additives for the resolution of chiral substances. Background technique [0002] In the biological chiral environment, living substance molecules, drug molecules, and pesticide molecules with different chirality will show completely different physiological, pharmacological, and toxicological effects. In the pharmaceutical industry, about 30%-40% of the known drugs are photoactive chiral drugs. In the pesticide industry, all agricultural natural pesticides are optically active; 17% of synthetic pesticides are chiral pesticides. With the development of biochemistry and medicinal chemistry, there is an increasing demand for opt...

AI Technical Summary

Problems solved by technology

[0006] (1) There are three types of natural cyclodextrins: α-CD, β-CD and γ-CD: α-CD has a small molecular cavity, and usually can only contain small guest substances with a narrow range of applications; γ-CD The molecular hole is large and can include larger molecular objects, but the production cost of γ-CD is high, and it cannot be mass-produced industrially; the molecular hole size of β-CD is moderate to make it include a wide range of inclusions, and the production cost is low. It is currently the only cyclodextrin product produced on an industrial scale, but the low solubility of β-CD in water limits its application range

(2) The chiral recognition effect caused by β-CD itself is limited due to the geometric symmetry inside the cavity of β-CD

(3) β-CD itself is not charged, so as a chiral additive of HPCE, neutral substances cannot be separated

(4) Binary CD system, some people use binary CD system, including a highly sulfonated (α-, β-, γ-HSCD) and a neutral CD, any seven (2,3,6 -3-O-methyl)-β-CD (TMCD), seven (2,6-bis-O-methyl)-β-CD (DMCD) or hydroxypropyl-β-CD (HPCD), can be separated The results of 25 drugs with different acid-base properties (16 kinds of basic drugs, 8 kinds of acidic drugs, and 1 kind of neutral drugs) show that the binary CD system is very effective in separating chiral substances, but HP-CD alone cannot fully separate them ,

In addition, the toxicity of drugs is a combination of many factors, such as the selectivity of receptors, the in vivo process of drugs and their metabolites, and the selectivity of metabolites to side effects. Therefore, racemates and enantiomers, enantiomers and Enantiomers can vary widely in toxicity

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