Two-phase (w / O) Recognition Chiral Extraction Drug Enantiomers

In this paper,α-cyclohexyl-mandelic acid (α-CHMA) enantiomers and mandelic acid enantiomers were separated by a new chiral separation technique—two-phase (W/O) recognition chiral extraction. The main contents can be summarized as follows:1,Study on chiral extraction ofα-cyclohexyl-mandelic acid (α-CHMA) enantiomers and mandelic acid (MS) enantiomers. The preferentially chiral recognition ability of extractant (tartrate derivatives andβ-CD derivatives), the influence of the kind organic solute and concentration of extractant and pH on extraction performance was investigated. The experimental results indicate that two-phase (W/O) recognition chiral extraction is of strong chiral separation ability. HP-β-CD, HE-β-CD and Me-β-CD have higher recognition ability for S-enantiomers than that for R-enantiomers. But some tartaric-acid derivatives have reversed recognition ability for them. In the extraction system containing HP-β-CD and D-isobutyl tartrate, the extraction effect ofα-CHMA is optimum by one stage extraction, and the distribution ratio for R-CHMA(k_R) and for S-CHMA(k_S) and separation factor(α) are 2.44, 0.89 and 2.49, respectively. In the extraction system containing HP-β-CD and di-O, O'-P-toluyl-D-tartaric acid, the extraction effect of MS is optimum by one stage extraction, and the distribution ratio for R-MS(k_R) and for S-MS(k_S) and separation factor(α) are 2.11, 1.38 and 1.53, respectively. Meanwhile, pH and concentration of extractants have great effects on chiral separation ability.2,Study on inclusion betweenβ-cyclodextrin derivatives andα-cyclohexyl-mandelic acid and mandelic acid, respectively. The inclusion stability constants ofβ-cyclodextrin derivatives ( HP-β-CD,HE-β-CD,Me-β-CD) withα-cyclohexyl-mandelic acid and mandelic acid were studied using UV spectrophotometry. Inclusion formation constants,the effects of alcohol and ironic strength on inclusion behavior were further investigated. The experimental results indicate allβ-cyclodextrin derivatives had weak binding ability withα-cyclohexyl-mandelic acid and mandelic acid in aqueous solution and host-guest complex with 1:1 molar ratio is formed;△G,△H and△S of those binding reaction are all less than 0, so the inclusion process is a spontaneous and exothermic process, and lower temperature is of benefit to reaction; Ionic strength greatly influence on binding ability of HP-β-CD with CHMA. Strong ionic strength is good for reaction; Increasing of alcohol concentration is in favor of inclusion between HP-β-CD with CHMA, whereas, is bad for that of HP-β-CD with MS.