The Research Of Racemization Chiral Drugs

Raceme drugs are made up of different enantiomers,usually one of them is active,and the other is invalid even harmful.Therefore,to obtain single enantiomer has been an imminent task in modern medicine industry.Now two different architectonic enantiomers could be effectively separated via resolution by medicine industry.It's so waste to throw away directly,so this invalid even harmful enantiomer could be racemated,then resoluted in order to recycle and save cost,thus to improve resolution efficiency.It makes important application value in large-scale industrialized production.Ondansetron is main component of prefer medicine to cure cytotoxic drug chemotherapy and postoperative nausea vomitory,while 2-Chloromandelic acid is an important intermediate of clopidogrel.Our group have already studied their technical process,so this essay studied their racemation.We use classic orthogonal methods through series of experiments on conditions of alkali,solvent,quantity of alkali,time,temperature and so on.At last,we obtain optimal racemation technical conditions:ondansetron: methanol is the best solvent,NaOH is alkali,0.5 times quantity of alkali and refluence reaction 20min;2-Chloromandelic acid: DMSO is the best solvent,NaOH is alkali,2 times quantity of alkali and refluence reaction 2 hours in 160?.Besides,we try to study the racemation mechanism and propose homologous racemtion mechanism of them.Ondansetron: the proton at the stereogenic center of could be removed by strong alkalinity to form carbanion.Carbonyl between carbon atom that close together led to enol tautomerization to form carbon double bond conjugated with benzene ring to form flane structure,which chiral carbon atom change sp3 hybridization to sp2.Protonation of the planar carbanion or alkene would definitely produce a racemic compound due to equal probabilities of access of the proton on both faces of the plane.2-Chloromandelic acid: the proton at the stereogenic center of could be removed by strong alkalinity to form carbanion.A more stable five-membered ring could be formed through a hydrogen bond between hydroxyl and carboxyl with olefine ketone tautomerization,carbon double bond conjugated with benzene ring to form flane structure.Protonation of the planar carbanion or alkene would definitely produce a racemic compound due to equal probabilities of access of the proton on both faces of the plane.