- Preparation method of anti-form cefuroxime derivative
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The invention relates to a preparation method of an anti-form cefuroxime derivative. The preparation method comprises the steps that A, phosphorus pentachloride is dissolved in a solvent, in the presence of an acidamide reagent, cis-form methoxyiminofurylacetic acid amonium salt is added, and through a reaction, a cis-form methoxy-imino furan acetyl chloride solution is obtained; B, a solvent is added to the cis-form methoxy-imino furan acetyl chloride solution, then strong acid or strong base is added, stirring is conducted, and the cis-form methoxy-imino furan acetyl chloride solution is converted into anti-form methoxy-imino furan acetyl chloride. According to the preparation method of the anti-form cefuroxime derivative, on the basis of original preparation of the anti-form methoxy-imino furan acetyl chloride, an innovative method is provided, by adding a proper quantity of solvent, in the presence of the strong acid or strong base, cis-trans isomerism conversion is conducted, andaccordingly the high-purity anti-form cefuroxime derivative can be efficiently prepared through a synthesis method.
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- Process for the preparation of cefuroxime
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There is described a process for the preparation of cefuroxime from predominantly S-cefuroxime axetil, R, S mixture of cefuroxime axetil or R-cefuroxime axetil not meeting the purity criteria. This comprises treating cefuroxime axetil with alkoxides in the presence of a suitable solvent or solvent mixture and isolating cefuroxime from the reaction mixture.
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- Photoisomerization kinetics of cefuroxime axetil and related compounds
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The photoisomerization kinetics of aqueous solutions of cefuroxime axetil under irradiation at 254 nm was investigated by HPLC. The overall degradation is the result of a competition between the isomerization of the alkoxyimino group and the photolysis of the β-lactam ring. Cefuroxime axetil exists as a mixture of two diastereomers which are shown to react at different rates. This is true not only for the photoisomerization step but also for ground- state hydrolysis in alkaline conditions. Photoisomerization of the alkoxyimino group is also observed for the anti isomer of cefuroxime axetil and for some of its degradation products. The quantum yields for all these photoisomerizations are always lower than 1%, which explains the relative importance of the photolysis step. A stationary syn to anti ratio of 1 is measured for cefuroxime axetil and of 2.1 for cefuroxime. From this and previous studies, it appears that cefuroxime axetil is the most sensitive under irradiation at 254 nm when compared to other antibiotics bearing the alkoxyimino group. Aztreonam is the most stable followed by cefotaxime, cefuroxime, and cefuroxime axetil.
- Fabre,Ibork,Lerner
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p. 553 - 558
(2007/10/02)
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- Prodrug derivatives of carboxylic acid drugs
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Novel ester derivatives of carboxylic acid medicaments of formula (I), wherein R--COO--represents the acyloxy residue of a carboxylic acid drug or medicament, n is an integrer from 1 to 3, and R1 and R2 are the same or different and are selected from a group consisting of an alkyl, an alkenyl, an aryl, an aralkyl, a cycloalkyl and which group may be unsubstituted or substituted, or R1 and R2 together with the N forms a 4-, 5-, 6- or 7-membered heterocyclic ring, which in addition to the nitrogen atom may contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and which heterocyclic group may be substituted. These compounds are highly biolabile prodrug forms of the corresponding carboxylic acid compounds and are highly susceptible to undergoing enzymatic hydrolysis in vivo whereas they are highly stable in aqueous solution. The novel derivatives are less irritating to mucosa than the parent carboxylic acids and may provide an improved bio-availability of the drugs.
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- Process for the preparation of cephalosporin compounds
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A process for the preparation of a 3-carbamoyloxymethyl cephalosporin compound which comprises hydrolyzing a 3-phosphonocarbamoyloxymethyl cephalosporin compound. The hydrolysis is preferably effected at a pH in the range of pH3 to 4, for example using aqueous sodium hydrogen carbonate.
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