34876-35-2

Usage

Uses

Used in Pharmaceutical Industry:
3-Hydroxy-4-Methyl-2(5H)-thiophenone is used as an impurity reference substance for the identification and quantification of degradation products in the manufacturing and quality control processes of antibiotics, specifically Cephalexin (C256800) and Cefaclor (C235250). Its role is crucial in ensuring the safety, efficacy, and quality of these antibiotics.
As an acid degradation product, 3-Hydroxy-4-Methyl-2(5H)-thiophenone serves as a reference for understanding the stability and degradation pathways of Cephalexin and Cefaclor under various conditions. This information is vital for the development of robust manufacturing processes and the establishment of appropriate storage and handling guidelines to maintain the integrity and potency of these antibiotics.

Upstream product

• 15686-71-2 cefalexin 
• 50370-12-2 cefadroxil 
• 616-44-4 3-Methylthiophene 
• 31461-05-9 (6R)-3-methyl-8-oxo-7t-(trimethylsilanyl-amino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid trimethylsilanyl ester 
• 30959-67-2 Cefradine 
• 57872-62-5 N-tert-butyloxycarbonylcefradine 

Relevant academic research and scientific papers

Dioxygenase-catalysed oxidation of monosubstituted thiophenes: sulfoxidation versus dihydrodiol formation.

Toluene dioxygenase (TDO)-catalysed sulfoxidation, using Pseudomonas putida UV4, was observed for the thiophene substrates 1A-1N. The unstable thiophene oxide metabolites, 6A-6G, 6K-6N, spontaneously dimerised yielding the corresponding racemic disulfoxide cycloadducts 7A-7G, 7K-7N. Dimeric or crossed [4 + 2] cycloaddition products, derived from the thiophene oxide intermediates 6A and 6D or 6B and 6D, were found when mixtures of thiophene substrates 1A and 1D or 1B and 1D were biotransformed. The thiophene sulfoxide metabolite 6B was also trapped as cycloadducts 17 or 18 using stable dienophiles. Preferential dioxygenase-catalysed oxidation of the substituent on the thiophene ring, including exocyclic sulfoxidation (1H-1J) and cis-dihydroxylation of a phenyl substituent (1G and 1N), was also observed. An enzyme-catalysed deoxygenation of a sulfoxide in P. putida UV4 was noticed when racemic disulfoxide cyclo-adducts 7A, 7B and 7K were converted to the corresponding enantioenriched monosulfoxides 8A, 8B and 8K via a kinetic resolution process. The parent thiophene 1A and the 3-substituted thiophenes 1K-1N were also found to undergo ring dihydroxylation yielding the cis/trans-dihydrodiol metabolites 9A and 9K-9N. Evidence is provided for a dehydrogenase-catalysed desaturation of a heterocyclic dihydrodiol (9Kcis/9Ktrans) to yield the corresponding 2,3-dihydroxythiophene (24) as its preferred thiolactone tautomer (23). A simple model to allow prediction of the structure of metabolites, formed from TDO-catalysed bacterial oxidation of thiophene substrates 1, is presented.

Synthesis of potential impurities of cefalexin and cefradine

The synthesis of some impurities of the cephalosporin antibiotics cefalexin and cefradine is described. These impurities which may be present in commercial samples are formed during the semi-synthetic preparation of these antibiotics or upon their degradation. The preparation of these compounds enables the validation of selective quantitative analytical methods, such as column liquid chromatography and thin layer chromatography.

Synthesis of related substances of cefadroxil

The chemical synthesis of some related substances of the cephalosporin antibiotic cefadroxil is described. These compounds which may be present in commercial samples originate from the semisynthetic preparation of the antibiotic or from degradation. The preparation of these products enables the validation of selective quantitative analytical methods, such as liquid chromatography and tlc.