Study On Drug Enantioseparation With High Selectivity Based On Co-Technology Of Bubble Fractionation And Solvent Extraction

In this paper, a co-technology of bubble fractionation and solvent extraction was developed for the enantioseparation of racemic typtophan (rac Trp) and α-Cyclohexyl-mandelic acid(rac a-CHMA) on the basis of our group’s previous work, and a preliminary investigation has also been carried out on the enantioselectivities and the theory of the separation. The main contents can be summarized as follows:(1) A co-technology of bubble fractionation and solvent extraction was used to separation the rac Trp. In this method, dibenzoyl-tartaric acid (X-DBTA) and di-(2-ethylhexyl) phosphoric acid (D2EHPA), sodium laury sulfate (SDS) were used as chiral co-extractants and foamer, respectively. Several important parameters influencing the separation performances, such as pH in aqueous phase, concentrations of rac mixtures, L-DBTA, D2EHPA and SDS were investigated. The enantiomeric excess and separation factor were65.09%and6.31under the optimal operation conditions, which were obtained with the aqueous phase pH6.0, temperature of20℃, reflux time4h, concentration of L-(-)DBTA0.20g/mL, rac Trp1.40mg/mL, SDS0.06mg/mL, D2EHPA1.51mol/L and the volumn of organic and aqueous were20mL and120mL respectively.(2) A novel separation technology, bubble fractionation, was developed for the enantioseparation of rac α-CHMA. The experiment was carried out in a conventional bubble column using D-iso-butyl tartrate (D-IBTA) and sodium laury sulfate (SDS) as chiral selector and surfactant, respectively. Several important parameters influencing the separation performance, such as pH in aqueous phase, concentrations of CHMA, D-IBTA and SDS were investigated. The results showed the enantiomeric excess and enantioselectivity were54.85%and4.5with the aqueous pH3.8, temperature of20℃, reflux time4h, concentration of D-IBTA0.30mol/L, rac CHMA0.30mg/mL, SDS0.65mg/mL, and the volumn of organic and aqueous were20mL and120mL respectively. (3) The separation process, thermodynamic and kinetic properties of separation were investigated, which indicates an enthalpy-controlled process and an obedience to the first order kinetics.