Erythromycin a oxime 11,12-carbonate and its oxime ethers.

Abstract

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.

Structural and conformational analysis of (E)‐erythromycin A oxime

“…A spatial proximity map was built from the observed NOEs found in 2D phase-sensitive 'H NOESY and 1D 'H NOE difference experiments (see Table 3). " The intra-lactone interactions of [11]4, [ll]7ax, [11]6-OH, [4]21 and [10]7,, NOEs are indicative of the close cross-ring proximity of these protons in solution. Additionally, a very small [11]3 NOE is observed.…”

Synthesis, ($E)$/($Z)$-isomerization, and DNA binding, antibacterial, and antifungal activities of novel oximes and $O$-substituted oxime ethers

“…Oximes and O -substituted oxime ethers are important compounds in medicinal chemistry as potent pharmacophores 1−3 and building blocks of drug scaffolds. 4,5 They are gaining interest as antiprotozoan, 6 antibacterial, 7 antiretroviral, 8 antifungal, 9,10 antineoplastic, 11 and antimicrobial agents. 12 These are also serving as antidotes for organophosphorus poisoning.…”

“…4,5 They are gaining interest as antiprotozoan, 6 antibacterial, tetradecanoic acid methyl esters) (3a-3d), and O -benzyl oxime ethers (benzyloxyimino-tetradecanoic acid methyl esters) (4a-4d). These twelve novel compounds were analyzed for their structures and isomerizations (( E)/( Z) ratio) by 1 H and 13 C NMR, FT-IR, mass, and elemental analyses.…”

Synthesis and Antimicrobial Activity of Some New Flavonyl Oxime Ether Derivatives

“…The field of biological activity of these analogues is rather wide, ranging from antibacterial [2] and antiviral [3−8] to vasoprotective, spasmolytic and antihepatotoxic activity [9−11]. On the other hand, the oxime ether derivatives of erythromycin [12] and cephalosporins [13−17] have been prepared and it was reported that these compounds have shown potent antibacterial activity. Following these observations, we 2.…”