Studies on the biosynthesis of clavulanic acid. Part 4. Synthetic routes to the monocyclic β-lactam precursor, proclavaminic acid

Baggaley, Keith H.; Elson, Stephen W.; Nicholson, Neville; Sime, John T.

doi:10.1039/p19900001513

Cited by 18 publications

(14 citation statements)

References 21 publications

(13 reference statements)

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“…[36,37] N-benzylazetidinone and sodium oxazetidinylacetate (Na(oaa)) were synthesized according to published procedures; [50,51] analytical data for Na(oaa): . Solvents were dried according to established procedures; penicillin G sodium salt and cephalothin were purchased from Sigma; all other chemicals were purchased from commercial sources and used as-received.…”

Section: Methodsmentioning

confidence: 99%

Biomimetic Hydrolysis of Penicillin G Catalyzed by Dinuclear Zinc(II) Complexes: Structure–Activity Correlations in β‐Lactamase Model Systems

Bauer‐Siebenlist

Dechert

Meyer

2005

Chemistry A European J

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A series of highly preorganized pyrazolate-based dinuclear zinc complexes has been studied as functional synthetic analogues of metallo-beta-lactamases, a class of bacterial enzymes that cause serious clinical problems because of their degradation of common beta-lactam antibiotics. We have investigated the hydrolytic cleavage of penicillin G mediated by the different dinuclear zinc complexes, and have deduced structure-activity correlations. While cooperative effects of the adjacent metal ions might be operative, these are found to either enhance or diminish beta-lactamase activity with respect to a single free zinc. Drastic differences in activity are ascribed to a lack of accessible binding sites after incorporation of the substrate within the bimetallic pocket of 2 and 4, whereas partial detachment of hemilabile ligand side arms in 1 and 3 opens up available coordination sites for nucleophile activation and/or for binding and polarisation of the beta-lactam amide oxygen atom. This interpretation has been corroborated by NMR spectroscopic and mass spectrometric evidence as well as by X-ray crystallography of several adducts formed between the pyrazolate-based dinuclear zinc scaffolds and the small substrate analogue oxazetidinylacetate (oaa), 5-7. In all adducts, the carboxylate group of oaa is the primary anchoring site and is nested in a bridging position within the bimetallic pocket. However, zinc binding of the beta-lactam amide oxygen atom has been confirmed crystallographically for the first time in 7, in which additional open-site coordination sites are available.

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Section: Methodsmentioning

confidence: 99%

Biomimetic Hydrolysis of Penicillin G Catalyzed by Dinuclear Zinc(II) Complexes: Structure–Activity Correlations in β‐Lactamase Model Systems

Bauer‐Siebenlist

Dechert

Meyer

2005

Chemistry A European J

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“…No espectro de RMN 1 H (anexo 3) foi possível obter dados sobre os deslocamentos de hidrogênio do composto A2G5B e em comparação com os dados da literatura foi possível correlacioná-lo com o ácido proclavamínico (Figura 26) (BAGGALEY et al,1990). Na tabela 3, verificamos os valores de RMN 1 H do composto isolado (600 MHz) e do estudo de BAGGALEY et al, 1990 (400 MHz).…”

Section: Diante Desta Informação Foi Realizada Uma Busca No Banco Deunclassified

“…Posição do H A2G5B Baggaley et al,(1990) δH, multiplicidade e J (Hz) δH, multiplicidade e J (Hz) (BAGGALEY et al, 1990).…”

Section: áCido Proclavamínicounclassified

“…O ácido proclavamínico foi o primeiro intermediário na via biossintética do ácido clavulânico a ser identificado. O uso do ácido proclavamínico como substrato e da enzima clavaminato sintase (CAS) foi capaz de gerar o ácido clavamínico (BAGGALEY et al, 1990;OLIVEIRA et al, 1994).…”

Section: áCido Proclavamínicounclassified

“…A conversão do ácido clavamínico em ácido clavulânico implica em modificações na cadeia lateral, assim como a inversão da estereoquímica do anel. O ácido clavulânico é constituído por um anel β-lactâmico condensado a um anel oxazolidina que age na inibição das β-lactamases produzidas pelas bactérias resistentes (BAGGALEY et al, 1990).…”

Section: áCido Proclavamínicounclassified

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Isolamento bioguiado de compostos de actinobactérias com atividade fungitóxica

Reis¹

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ChemInform Abstract: Studies on the Biosynthesis of Clavulanic Acid. Part 4. Synthetic Routes to the Monocyclic β‐Lactam Precursor, Proclavaminic Acid.

et al. 1990

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Studies on the biosynthesis of clavulanic acid. Part 4. Synthetic routes to the monocyclic β-lactam precursor, proclavaminic acid

Cited by 18 publications

References 21 publications

Biomimetic Hydrolysis of Penicillin G Catalyzed by Dinuclear Zinc(II) Complexes: Structure–Activity Correlations in β‐Lactamase Model Systems

Biomimetic Hydrolysis of Penicillin G Catalyzed by Dinuclear Zinc(II) Complexes: Structure–Activity Correlations in β‐Lactamase Model Systems

Isolamento bioguiado de compostos de actinobactérias com atividade fungitóxica

ChemInform Abstract: Studies on the Biosynthesis of Clavulanic Acid. Part 4. Synthetic Routes to the Monocyclic β‐Lactam Precursor, Proclavaminic Acid.

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