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Dirithromycin (3) isomerizes upon dissolution in different solvents. From X-ray analysis of V-T 108, an analogue of dirithromycin, and comparative 1H and 13C NMR,and MSdata, the isomer ofdirithromycin was confirmed to be the C-16-(S)-epimer. The ratio of the two epimers at equilibrium conditions was approximately 8 : 2 (R/S) in methanol at room temperature.To improve the therapeutic properties of erythromycin, a series of tetrahydro-l,3-oxazines 2 was synthesized by condensation of 9(S)-erythromycylamine 1 with substituted acetaldehydes1*. From these, dirithromycin (3) (2, R= CH3OCH2CH2O-)was selected for further investigations. The structure of 3 was confirmed by X-ray analysis2). Thereby, the (^-configuration of the newly introduced chiral center at C-16 could be established in dirithromycin. Preliminary ObservationsCrystallization of the condensation product of 1 with 2-methoxyethoxyacetaldehyde from acetonitrile gave pure 3, as determined by X-ray analysis and *H NMRspectra. Dissolution of 3 in different solvents leads to an equilibrium of 3 with a new compound3a, detected by TLC. The rate of formation of 3a depends on solvent, time, and temperature.*H NMRinvestigations showed the equilibration rate in methanol to be low (approx 5%within 24 hours) compared to other solvents as acetone, chloroform or toluene. The ratio of3 to 3a at equilibrium conditions at room temperature was estimated to be approximately 8 : 2. The isolation of pure 3a by TLC failed because rechromatography of the isolated spot revealed again

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