Chirality Preparation Of Ondansetron Hydrochloride

Different configurations of chiral drugs have different activities in vivo metabolism rate,metabolism process,physiological activity and toxicity.Chiral drugs could be result in augmentation of potency,or reduction even elimination of drug's toxic and side-effect,or creation of new pharmaco-effect.This indicates that the research of chiral drugs has great significance not only on clinic dosage,but also on domain of new drugs development.Ondansetron is a 1,2,3,9-Tetrahydro-4H-Carbazol-4-One derivative,which has one chiral carbon center and two configurations R and S.Ondansetron is preferred to be used for nausea and vomiting,which are mainly caused by chemotherapy or radiotherapy.It has many advantages such as:high selectivity,little side-effect,swift oral absorption and so on.It is reported that the two different configurations have different vivo metabolism acivity.Therefore,research of chiral ondansetron has great point on economy and practice.There are few reports about chiral separation of ondansetron,mainly centerred on chromatogram.Now we plan to choose tartaric acid derivatives as resolving agent for resolution of orgno-amine drug ondansetron.We use classic chemistry resolution and group resolution methods through series of experiments on conditions of resolving agent,solvent,way of precipitation,cooling time,rate of host and subject,recrystallisation solvent and so on.At last,we choose the best condition of resolution:DTTA is the best resolving agent,and THF and water mixing system is the best resolution solvent,then we could obtain pure optical chiral ondansetron after recrystallizing and dissociating.In addition,we try to analyze through 1HNMR,DSC\TGA,infrared and X-ray powder diffraction to obtain more effictive information,thus to research on the resolution mechanism,and make some comparison on the two diastereomer salts of ondansetron.