Oxime-mediated facile access to 5-methylisoxazoles and applications in the synthesis of valdecoxib and oxacillin.

A palladium-catalyzed efficient synthesis of 5-methylisoxazoles via oxime-mediated functionalization of unactivated olefins is described. The reaction affords a variety of 5-methylisoxazoles in moderate to good yields. To further demonstrate the utility of the method, the rapid synthesis of valdecoxib and oxacillin is reported.

[Research for the improvement of acylation conditions in antistaphylococcal penicillin synthesis]. / Cercetari privind îmbunatatirea conditiilor de acilare în cazul obtinerii penicilinelor antistafilococice.

AIM: The 6-aminopenicillanic acid acylation with certain acyl chlorides was performed in order to obtain antistaphylococcal penicillins with bigger crystals, easy to filtrate (shorter filtration time), much pure, and an increased output. MATERIAL AND METHODS: Oxacillin sodium salt was synthesized by acylating an aqueous solution of 6-aminopenicillanic acid sodium salt (NaHCO3 not in excess) with an ethylacetate solution of 5-phenyl-3-methyl-isoxazolyl-4-carboxilic acid chloride. The crystallization was performed with a 40.5% sodium 2-ethyl hexanoate izopropanolic solution. All tests (IR spectrum, iodometric titration, and microbiological dosage) were performed according to the Xth Romanian Pharmacopoeia standards. RESULTS: The amount of synthesized oxacillin was higher and the output of 88,21%. Oxacillin had a high chemical purity (98,72%), and a very good microbiological activity (95% of the standard activity). CONCLUSIONS: Oxacillin crystals were bigger, the filtration speed was increased, and process efficacy improved. The output of the process was also improved being higher than with classical acylation.

Water mediated construction of trisubstituted pyrazoles/isoxazoles library using ketene dithioacetals.

A small molecule library of alkyl, sulfone, and carboxamide functionalized pyrazoles and isoxazoles has been developed via a rapid sequential condensation of various alpha-acylketene dithioacetals (1a-o) with hydrazine hydrate or hydroxylamine hydrochloride, followed by oxidation of sulfide to sulfone using water as the reaction medium. An efficient and safe oxidation of sulfides (4/5a-o) to the corresponding sulfones (6/7a-o) using sodium per borate system in aqueous medium is reported. The concise and two step synthesis of trisubstituted pyrazoles and isoxazoles was investigated under variety of reaction condition. The newly developed methodology has the advantage of excellent yield and chemical purity with short reaction time using water as a solvent.

[A method of quality control of 3-phenyl-5-methylisoxazole-4-carbonic acid chloranhydride using high performance liquid chromatography]. / Metod kontrolia kachestva khlorangidrida 3-fenil-5-metilizoksazol-4-karbonovoi kisloty s pomoshch'iu vysokoéffektivnoi zhidkostnoi khromatografii.

A method of quantitative determination of 3-phenyl-5-methyl-isoxazole-4-carbonyl chloride useful for its qualitative estimation at all stages of oxacillin industrial synthesis was developed. The methods is based on transformation of this semi-product into isopropyl ester followed by high efficiency liquid chromatography with the use of the "Milikhrom" chromatograph mad in the USSR. A variant of the typical method for determination of 3-phenyl-5-methyl-isoxazole-4-carbonyl chloride concentration in solution is described.

[Studies reagarding the bioavailability of oxacillin from preconditioned powders]. / Cercetari privind biodisponibilitatea oxacilinei din pulberi prieconditionate.

Previous studies have pointed out a good antimicrobial activity of two oxacillin salts--DBED--oxacillin and calcic oxacillin--which were conditioned as "preconditioned powders" for oral suspensions. The above mentioned preparations were followed up by administration to animals, and similar seric concentrations in DBED oxacillin and sodic oxacillin (with the difference that insoluble salts present a long-time activity) were pointed out.

[Isoxazolylpenicillins with cycloaliphatic substituents in the isoxazole ring]. / Isossazolilpenicilline con sostituenti cicloalifatici nel nucleo isossazolico

Some derivatives of oxacillin were prepared containing in place of the phenyl group a cyclohexyl, cyclohexylphenyl, phenylcyclohexyl or diphenylyl moiety. In the same compounds a methylene bridge between the carboxy group and the heterocyclic ring was inserted. The results of in vitro evaluation of antibacterial activity are given.