Bis[6-oxygen-(2-m-carboxylbenzene Sulfonyl-amber Acid-1,4 Uniester-4)]-β-CD Was Applied To Separate Chiral Drug In HPCE

This paper outlined the effect of enantiomeric separation in chiral compoundes and effect of chiral separation withβ-cyclodextrin(abbr.β-CD) andβ-CD derivatives. The application ofβ-CD andβ-CD derivatives in HPCE as chiral selector was introduced. Bis[6-oxygen-(2-m- carboxylbenzene sulfonyl-amber acid-1,4 uniester-4)]-β-CD (abbr.β-CD-B₂) was synthesized. The reaction conditions were optimized. The synthesizedβ-CD-B₂ was separated and purified. The goal derivative was confirmed by characterization with Fourier transform infrared spectra, ultraviolet map scanning, XRD, elemental analysis, 13C NMR, HSQC, HMBC, and MS. It had not been seen on literature report.DL-2-Phenylglycinol enantiomer was successfully recognized byβ-CD-B₂ as chiral selector in HPCE. The effect of concentration ofβ-CD-B₂ on resolution was studied. The effects of other parameters on resolution were also investigated, such as pH, buffer concentration, applied voltage, and optimized the separation conditions. The baseline resolution of DL-2-Phenylglycinol enantiomer can be achieved by using 50mM Tris-H₃PO₄ buffer at pH4.5 containing 7g/Lβ-CD-B₂, the voltage was 25kV in the wavelength 254nm. The lineared extent of the mono D-2-Phenylglycinol and mono L-2-Phenylglycinol were affirmed. A good linear correlation of mono D-2-Phenylglycinol (tR =11.47-12.57min) was100-300mmol/L (r=0.992), and mono L-2-Phenylglycinol (tR=3.68-3.97min) was 100-400mmol/L (r=0.999). In DL-2-Phenylglycinol antimer, a good linear correlation of D-2-Phenylglycinol was 200-500mmol/L (r=0.992) and L-2-Phenylglycinol was 50-300mmol/L (r=0.988). Mechanism of action was discussed.Five chiral drug were separated byβ-CD-B₂ as chiral selector in HPCE, such as anisodamine, isoproterenol, chlorpheniramine, bupivacaine, propafenone. Different chiral selector (β-CD,β-CD-A₂,β-CD-B₂) were discussed. It is displayed by the experiment consequence that the chiral recognition ofβ-CD-B₂ was better than others. The other parameters were also researched. Through the optimization of the separation conditions, Best separation conditions of five chiral drugs had been discovered by HPCE. Meanwhile, the maximum resolution power of anisodamine (Rs=1.86), isoproterenol (Rs=2.46), chlorpheniramine (Rs=1.10), bupivacaine (Rs=1.80), propafenone (Rs=3.36), anisodamine and isoproterenol were qualitatively analyzed by their standard substance. The mechanism of enantioselectivity was discussed. There are synergism of clathration, hydrogen bond, hyperconjugation and electrostatic interaction betweenβ-CD-B₂ and chiral drug. Anisodamine was separated by electrostatic interaction; the others were recognized by synergism of clathration, hydrogen bond, hyperconjugation.