SYNTHESIS OF OXAZOLIDINES FROM EPHEDRINES AS POTENTIAL PRODRUGS

Twenty three (-) - or (+)- 2 - (substituted phenyl )- 3,4 - dimethyl -5 - phenyl - oxazolidines and five Schiff base derivatives of ephedrine were synthesized bycyclization or condensation with aromatic aldehydes, according to the structure-activityrelationships and the pro- drug principle. Stereochemical structures were studied for thesecompounds by spectroanalysis method, and the kinetics of hydrolysis of the oxazolidineswere also studied by UV spectra and HPLC methods. The oxazolidines were found to un-dergo a facile and complete hydrolysis at pH 7. 40 and 37℃ and the half-lives ofhydrolysis were determined. The relationship between structure and stability of the oxazolidine derivatives were discussed. The oxazolidine derivatives are more lipophilic andless basic than the parent ephedrines and their chemical and physical characters are morestable than those of the parent aromatic aldehydes. The stability of the oxazolidine deriva-tives is affected by the configurations of ephedrines and the positions or Hammett con-stants of the substituents in the aromatic aldehydes. These results indicate that oxazolidinescan be considered as potential prodrugs for ephedrines.