Structural and conformational analysis of (<i>E</i>)‐erythromycin A oxime

McGill, James M.; Johnson, Ross A.

doi:10.1002/mrc.1260310312

Cited by 16 publications

(2 citation statements)

References 19 publications

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“…The assignments with the earlier assigned values 9 agree with one another to within š0.10 ppm for all the 1 H resonances except the resonances of desosamine sugar because of the conversion of (-N(CH 3 ) 2 to -N(CH 3 ) 2 H C Cl in the mixture, which was confirmed in the isolated product after separation and are shown in Tables 1 and 2. The remaining 1 H and 13 C NMR signals were then utilized for the assignments of the other three byproducts.…”

Section: Resultssupporting

confidence: 56%

Translactonization of erythromycin A during oximation: mixture analysis and reaction monitoring by NMR

Grover¹,

Joshi²,

Batra³

et al. 2001

Magnetic Reson in Chemistry

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Oximation of erythromycin A with hydroxylamine hydrochloride and sodium acetate in methanol led to the formation of pseudoerythromycin A enol ether with erythromycin A oxime as analysed by detailed two-dimensional NMR spectroscopy in the mixture along with traces of 8,9-anhydroerythromycin A 6,9-hemiketal and erythromycin A 6,9:9,12-spiroketal. The formation of the degraded products was established by performing in situ 13 C NMR spectroscopy. The analysis suggests that pseudoerythromycin A enol ether is formed by the translactonization of erythromycin A enol ether which forms as a result of acid degradation.

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Section: Resultssupporting

confidence: 56%

Translactonization of erythromycin A during oximation: mixture analysis and reaction monitoring by NMR

Grover¹,

Joshi²,

Batra³

et al. 2001

Magnetic Reson in Chemistry

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“…With the exception of hydroxylamine (E/Z ) 5/1), this reaction gave predominantly the E isomers. The E stereochemistry of these oximes was established by comparison of previous studies 4b, 34 that demonstrated that the H 8 proton of (E)-oximes was deshielded to ∼3.75 ppm. This characteristic was conserved in our structures ( Table 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antibacterial Activity of Ketolides (6-O-Methyl-3-oxoerythromycin Derivatives): A New Class of Antibacterials Highly Potent Against Macrolide-Resistant and -Susceptible Respiratory Pathogens

Agouridas¹,

Denis²,

Auger³

et al. 1998

J. Med. Chem.

204

122

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In the search for new antibiotics active against macrolide-resistant pneumococci and Haemophilus influenzae, we synthesized a new class of 3-oxo-6-O-methylerythromycin derivatives, so-called "ketolides". A keto function was introduced in position 3 after removal of L-cladinose, a sugar which has long been thought essential. Further modifications of the macrolactone backbone allowed us to obtain three different series of 9-oxime, 11,12-carbamate, and 11, 12-hydrazonocarbamate ketolides. These compounds were found to be very active against penicillin/erythromycin-resistant pneumococci and noninducers of MLSB resistance. The 11,12-substituted ketolide 61 (HMR 3004) demonstrated a potent activity against multiresistant pneumococci associated with a well-balanced activity against all bacteria involved in respiratory infections including H. influenzae, Mycoplasma catarrhalis, group A streptococci, and atypical bacteria. In addition HMR 3004 displayed high therapeutic activity in animals infected by all major strains, irrespective of their resistance phenotype.

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Conformation of Deoxy Oligosaccharides: Solution Conformation and Flexibility of the Antibiotic Kijanimicin Studied by NMR Spectroscopy and MMC Calculations

Köpper

1994

Liebigs Ann. Chem.

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The solution conformation of the macrolide antibiotic kijanimicin (1) was deduced by a combination of NMR spectroscopy and potential energy calculations of the carbohydrate parts using the HSEA force field. The study was based on temperature dependent NMR spectroscopic shift data, 1D nuclear Overhauser enhancements (NOE) of selected protons and 2D rotating frame NOE of the complete antibiotic. NOEs in the oligosaccharide part of the antibiotic indicated some unusual short distances between the a-linked digitoxose residues A and B, as well as between not directly linked residues A and C. Calculation of preferred conformations revealed a global minimum with @A,B/YA,B = 70"/50', @B,C/ YB,c = 60"/30", and @B,D/YB,D = -60"/5' for the oligosaccharide moiety. MMC simulations of the conformational flexibility indicated a high rigidity of the carbohydrate. The range of the glycosidic angles covered during MMC simulations was 5Oo-7O0 for the a-linkages of the oligosaccharide. The pglycosidic linkages of residue D and E showed slightly more flexibility, covering a range of 12O0-27Oo. Minimum energy calculations of the oligosaccharide part revealed a second minimum with different orientation of sugar residues A-B and an energy difference of 2 kcaVmol to the global minimum. This energy difference increased to 12 kcaVmol when the complete antibiotic was calculated and MMC simulations did not show any transitions between the two minima. The experimental NOE in the oligosaccharide moiety and the enhancements between carbohydrate and lactone part agree well with theoretical NOEs that were obtained by sampling the global minimum in MMC simulations. The conformation of the macrolide moiety was evaluated by comparing experimental NOEs with the crystal structure of the isolated aglycon. The conformation found in solution is slightly altered around the sites of attachment of the carbohydrate parts. Constancy of the proton chemical shifts over a temperature range of 70°C indicated the high degree of rigidity of the carbohydrate moiety and most of the macrolide structure. Flexibility was observed for the C-13/C-20 part of the lactone ring. The antibiotic has a fairly unpolar surface and adopts a well defined and quite rigid conformation.

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

Cited by 16 publications

References 19 publications

Translactonization of erythromycin A during oximation: mixture analysis and reaction monitoring by NMR

Translactonization of erythromycin A during oximation: mixture analysis and reaction monitoring by NMR

Synthesis and Antibacterial Activity of Ketolides (6-O-Methyl-3-oxoerythromycin Derivatives): A New Class of Antibacterials Highly Potent Against Macrolide-Resistant and -Susceptible Respiratory Pathogens

Conformation of Deoxy Oligosaccharides: Solution Conformation and Flexibility of the Antibiotic Kijanimicin Studied by NMR Spectroscopy and MMC Calculations

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