Study On Enantioseparation Of Ofloxacin Through Chiral Liquid-liquid Extraction

As one of the third-generation fluoroquinolone antibacterial drugs,ofloxacin has been widely used in clinical process.The L-ofloxacin has minor side effects,smaller dosage and higher drug acitivity when compared with its racemate.Studies have shown that the antibacterial activity of L-ofloxacin is 8 to 128 times higher than that of D-ofloxacin and is twice as its racemate.Currently,the preparation of optical purity of L-ofloxacin by chiral enantioseparation is the focus.Chiral liquid-liquid extraction separation has attracted widespread attention in recent years based on its easily realizing industrialization,low energy consumption,simple equipment and mild operating conditions.In this dissertation,the separation process of ofloxacin racemate was studied by chiral liquid-liquid extraction.The main context is as follows:1.Acetic acid has been chosen as a cosolvent to improve the poor solubility and extraction capacity of ofloxacin and obtain a high concentration ofloxacin aqueous solution(>10000ppm).Using diethyl L-tartrate(L-TADE)as chiral extractant,effects of extraction temperature,and diethyl L-tartrate,acetic acid and ofloxacin enantiomer concentration of enantiseparation are investigated.When the concentration of diethyl L-tartaric,ofloxacin and acetic acid is 0.2mol/L,12000 ppm and O.lmol/L,respectively,the ofloxacin enantiomer chiral separation coefficient is 1.39 at 25 ?.The results show that both dissolution concentration of ofloxacin and enantioselectivity coefficient are improved compared with the previous work.And to better understand the experiment result from microscopic level,molecular dynamics simulations are carried out to analyse the interaction energy of the chiral extractant and ofloxacin enantiomers.2.To further improve the selectivity of the ofloxacin enantioseparation process,the mixture of diethyl L-tartrate and L-(-)-dibenzoyl tartaric acid(L-DBTA)has been used as a mixed extractant,and the condition of the extraction process are also optimized.When t=25?,c(L-TADE)=0.5mol/L,c(HAc)=0.1 mol/L,c(L-DBTA)=0.1 mol/L,c(ofloxacin)=8000ppm,selective coefficient reaches 1.58.The mixed extractant system showed better extraction effect than that of single extractant.3.The simulation experiment has been carried out by Aspen Plus to simulate the distillate separation process of diethyl tartrate and octyl alcohol.The parameters of the distillation process including plate number,feed position and reflux ratio are optimized.A vacuum distillation process is designed to improve the problem of high temperature,high price of the steam.And the pressure tower of different operating pressure is also analyzed.