Synthesis and biological activity of O56-substituted carboxyesters and carboxamides of teicoplanin aglycone.

Seneci, Pierfausto; Trani, Aldo; Ferrari, Pietro; Scotti, Roberto; Ciabatti, Romeo

doi:10.7164/antibiotics.45.1633

Cited by 8 publications

(5 citation statements)

References 8 publications

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“…However, their interaction with the membrane itself should be quite aspecific and, hence, not necessarily with the correct orientation which probably is attained with teicoplanin derivatives still bearing the hydrocarbon side chain. This argument is in accord with the higher hydrophobicity found for the aglycons in solvent partition experiments 9e. However the partition in the C 8 -stationary phase of HPLC column appears to favor the antibiotic still having its long hydrocarbon chain on the glycidic R 1 residue (see formula).…”

Section: Resultssupporting

confidence: 62%

“…Antibiotics and Their Behavior in Aqueous Solution . All compounds studied in this work have been already described . They can be divided in two major groups: those with the three glycidic residues still present ( 1a − f ) and those devoid of them, aglycons 2a − g .…”

Section: Resultsmentioning

confidence: 99%

“…Materials . Teicoplanin (component A2), 1a , and semisynthetic derivatives 1b − f and 2a − g were obtained from Dr. A. Malabarba of the Lepetit Research Center and have been already described . ADLAA (Backem Switzerland) and AALAA (Sigma) were used as received.…”

Section: Methodsmentioning

confidence: 99%

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Kinetics and Thermodynamics of Binding of a Model Tripeptide to Teicoplanin and Analogous Semisynthetic Antibiotics

et al. 1996

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The thermodynamics and kinetics of binding of model tripeptides epsilon-N-acetyl-alpha-N-dansyl-L-Lys-D-Ala-D-Ala (ADLAA) or alpha-N,epsilon-N-diacetyl-L-Lys-D-Ala-D-Ala (AALAA) to teicoplanin (1a) and a series of semisynthetic derivatives with (1b-f) or devoid of (2a-g) the glycidic side arms and modified at the terminal amino acids of the peptide backbone have been studied by fluorescence or UV spectroscopy. The binding process is suggested to occur via a two-step mechanism. The first, fast process is likely governed by an electrostatic interaction between the C- and N-termini of the peptide chain of the substrate and of the antibiotic, respectively, while the second slower one, accounts for the formation of the hydrogen bonds responsible of the major contribution to the overall binding energy. The binding constants with all modified derivatives are smaller than that with native teicoplanin. Larger modification of the overall binding constant are observed when the sugar residues are removed and, to a lower extent, when the N-terminus of the peptide chain is acylated. The kinetic process is very little affected by the modifications introduced.

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Section: Resultssupporting

confidence: 62%

Section: Resultsmentioning

confidence: 99%

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Kinetics and Thermodynamics of Binding of a Model Tripeptide to Teicoplanin and Analogous Semisynthetic Antibiotics

et al. 1996

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“…For those interested in the total synthesis of vancomycin, we note that it is possible to arrive at the protected aglycon 14 from the known aglycon of vancomycin 18 (Scheme ) . Following protection of the amine and the carboxylic acid as shown, the phenol of amino acid 4 of the aglycon can be selectively protected with p -methoxylbenzyl chloride and cesium carbonate in the presence of the other three phenols and the two alcohols to give 19 . The remaining phenols can then be alkylated with allyl bromide, and the benzylic alcohols can be acetylated.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Vancomycin from the Aglycon

1999

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Vancomycin-resistant bacterial strains pose a serious threat to human health. Efforts to overcome vancomycin resistance by modifying the natural product have shown that the carbohydrates help modulate biological activity. To explore the mechanisms by which the carbohydrates function, it would be useful to have access to vancomycin derivatives containing different disaccharides. We now describe the synthesis of vancomycin from a readily available protected aglycon. This chemistry lays the groundwork for wide-ranging investigations of the roles of the carbohydrates in the biological activity of vancomycin. Moreover, in developing methods to glycosylate vancomcyin, we have extended the utility of the sulfoxide glycosylation reaction considerably by making it possible to use unhindered esters as neighboring groups. The chemistry we describe may also have implications for how to improve some other glycosylation methods.

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“…** SAR of a series of O 56 -alkyl ethers [ Fig. 12(m)] 75 of TD carboxamides or esters was also established. No significant improvement in the binding and antibacterial properties relative to TD or parent amides and esters was observed.…”

Section: Derivatization Of Hydroxy Groupsmentioning

confidence: 99%