[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 by cyclization or condensation with aromatic aldehydes, according to the structure-activity relationships and the pro-drug principle. Stereochemical structures were studied for these compounds by spectroanalysis method, and the kinetics of hydrolysis of the oxazolidines were also studied by UV spectra and HPLC methods. The oxazolidines were found to undergo a facile and complete hydrolysis at pH 7.40 and 37 degrees C and the half-lives of hydrolysis were determined. The relationship between structure and stability of the oxazolidine derivatives were discussed. The oxazolidine derivatives are more lipophilic and less basic than the parent ephedrines and their chemical and physical characters are more stable than those of the parent aromatic aldehydes. The stability of the oxazolidine derivatives is affected by the configurations of ephedrines and the positions or Hammett constants of the substituents in the aromatic aldehydes. These results indicate that oxazolidines can be considered as potential prodrugs for ephedrines.