KETONE HEMIACETAL TAUTOMERISM IN ERYTHROMYCIN-A IN NONAQUEOUS SOLUTIONS - AN NMR SPECTROSCOPIC STUDY

NMR spectroscopic studies, including C-13 SIMPLE NMR, in a number of solvents, show that erythromycin A exists as a mixture of the 9-ketone (the predominant species), one 6,9-cyclic hemiacetal 3 (9-deoxo-6-deoxy-9-hydroxy-6,9-epoxyerythromycin A), and one 9,12-cyclic hemiacetal 2 (9-deoxo-12-deoxy-9-hydroxy-9,12-epoxyerythromycin A). Similar studies on the 4'',11-diacetate of erythromycin A, previously thought to be the 6,9-cyclic hemiacetal, show that this exists exclusively as the 9,12-cyclic hemiacetal 4 (9-deoxo-12-deoxy-9-hydroxy-9,12-epoxyerythromycin A 4'',11-diacetate) in CDCl3. The (9S) stereochemistry is proposed for 2, 3 and 4. The factors governing tautomerism in erythromycin A and its derivative are discussed.