Erythromycin A oxime 1 1,12-carbonate (5a) and its oxime ethers 5b~5p have been prepared and their antibacterial activities compared with those of erythromycin A (1) and.its 1 1,12-carbonate 2. The oxime 5a and many of its oxime ether derivatives showed good activity in vitro against Gram-positive and the morepermeable Gram-negative organisms, in some cases being even more active than the carbonate 2.Erythromycin A 1 1,12-carbonate (2), which is easily prepared from erythromycin A (1) and ethylene carbonate1}, shows excellent activity against Gram-positive organisms in vitro, being about twice as active as erythromycin itself. 1 1,12-Carbonates have also been described for various derivatives of erythromycin, including (9S)-9-dihydroerythromycin A2), (9S)-erythromycylamine A3), and (8S)-8-hydroxyerythromycin A4), and like the carbonate 2, some of these are quite active as antibacterials. We therefore became interested in extending this series to the 1 1,12-carbonates of erythromycin A oxime and its oxime ethers, in the hope that such compounds might have the good activity shown by 2 combined with the acid stability1" of the 9-oximino derivatives. In this paper we describe the preparation and antibacterial activities of the oxime 5a and the oxime ethers 5b~5p^.Our initial attempts to prepare the oxime 5a and the methoxime 5b by reaction of erythromycin A 1 Erythromycin Ais very unstable to dilute mineral acid8), and this property undoubtedly contributes to the rather poor pharmacokinetics of orally administered erythromycin base. Erythromycin A oxime (3) and its derivatives are muchmorestable to mineral acid6).n A note on molecular structure is in order here. Although erythromycin A ll,12-carbonate is represented as the hydroxy-ketone 2, in solution it exists largely as two tautomeric 6,9-hemiacetals1). This type of tautomerism is not observed for compounds 5a~5p.

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