- Clavulanic Acid and its Derivatives. Structure Elucidation of Clavulanic Acid and the Preparation of Dihydroclavulanic Acid, Isoclavulanic acid, Esters and Related Oxidation Products
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Clavulanic acid, a novel β-lactamase inhibitor from Streptomyces clavuligerus, has been shown to be Z-(2R,5R)-3-(β-hydroxyethylidene)-7-oxo-4-oxa-1-azabicycloheptane-2-carboxylic acid (1).The structure and absolute stereochemistry was confirmed by X-ray analysis of the p-nitrobenzyl and p-bromobenzyl esters, (14) and (15).The conversion of clavulanic acid into a variety of esters and acyl derivatives is described.An account of its isomerisation to the E isomer (30) and the formation of an oxetane (45) as a by-product of the photolysis of the phenacyl ester (18) is given.The reduction and oxidation of acid (1) under a variety of conditions has also been examined in detail.
- Brown, Allan G.,Corbett, David F.,Goodacre, Jennifer,Harbridge, John B.,Howarth, T. Trefor,et al.
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p. 635 - 650
(2007/10/02)
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- Oxidative Decarboxylation of Clavulanic Acid and Its 9-Methyl Ether
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The carboxy group of clavulanic acid has been replaced by a methoxy group, an acetoxy group, and a m-chlorobenzoyloxy group using standard methods for oxidative decarboxylation (electrolysis, reaction with lead tetra-acetate, and decarboxylative rearrangement of a diacyl peroxide, respectively).In an unexpected reaction, 9-O-methylclavulanic acid (20) reacted with p-chlorophenylselenenyl bromide and base to give 3-(p-chlorophenylseleno)-2-(2-methoxyethylidene)clavam (21).Refluxing a solution of compound (21) in toluene gave 3-hydroxy-2-(2-methoxyethylidene)clavam and b is(p-chlorophenyl)diselenide, the overall result being the replacement of the carboxy group in the acid (20) by a hydroxy group.In chloroform, this 3-hydroxyclavam exists predominantly as the ring-opened aldehyde.Possible mechanisms for the formation of the seleno derivative (21) and its decomposition in refluxing toluene are discussed.
- Brooks, Gerald,Hunt, Eric
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p. 2513 - 2518
(2007/10/02)
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- A new total synthesis of (±)-clavulanic acid
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Regioselective reactions at the terminal double bond of the racemic azetidinone dienylether (4), provides a source of clavulanic acid and several analogues.
- Bentley, Peter H.,Brooks, Gerald,Gilpin, Martin L.,Hunt, Eric
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p. 1889 - 1890
(2007/10/10)
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