The conformations of the macrolide antibiotics erythromycin A, azithromycin and clarithromycin in aqueous solution: a H-1 NMR study

The conformations of the macrolide antibiotics erythromycin A, clarithromyc in and azithromycin in aqueous solution have been determined. All three dru gs were found to exist predominantly in a "folded-out" conformation with th e sugars in the chair-chair up-up form. In the case of clarithromycin this result is in agreement with the published literature; previous reports sugg est that the erythromycin A sugars adopt boat conformations and that azithr omycin has a significant folded-in contribution. The discrepancies are disc ussed in full. Erythromycin A 9-ketone was found to be flexible in the C6-C 12 region. We present evidence for a new minor conformation (the 8-endo fol ded-out conformation) intermediate between the folded-out and folded-in con formations. Evidence for traces of other minor conformations is presented f or erythromycin and azithromycin, whereas clarithromycin is conformationall y very stable.