Possibilities to acylate 7-aminocephalosporanic acid to obtain some cephalosporins.

AIM: Acylation of 7-aminocephalosporanic acid with an adequate acyl chloride in order to obtain cefotaxime sodium salt. MATERIAL AND METHODS: Cefotaxime sodium salt was synthesized by acylating 7-amino cephalosporanic acid with 2-[2'-chloracetamidothiazole-4-yl]-2-(syn)-methoxy-imino acetic chloride in four steps. The melting point was determined, and IR spectral analysis and elemental analysis were performed to confirm cefotaxime structure. The quantitative determination was performed. RESULTS: The reaction conditions were established. The yield of the synthesis phases (73-80%) and actual yield (45-47%) were very good. The structure of the obtained cefotaxime sodium salt was confirmed by the IR spectral analysis and by elemental analysis (C, H, N). The melting point was 163 degrees C. The purity of the synthesized cefotaxime sodium salt was 98.9%. CONCLUSIONS: Cefotaxime sodium salt was synthesized by acylation of 7-aminocephalosporanic acid with 2-[2'-chloracetamidothiazole-4-yl]-2-(syn)-methoxy-imino acetic chloride, in aqueous solution, then transformed into sodium salt with sodium 2-ethylhexanoate. The method proved to be very good, yields were good, it is reproducible and simple, and does not involve high risks, so it is also safe.

[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.

[Erythromycin ethylsuccinate obtaining possibilities]. / Posibilitati de obtinere a etil-succinatului de eritromicina.

UNLABELLED: In this study we tried to improve the erythromycin ethylsuccinate obtaining, having in view to separate the erythromycin ester by crystallization in water. MATERIAL AND METHODS: The erythromycin acylation and the erythromycin ethylsuccinate crystallization were realized, following the next steps: 1. the acylation of the erythromycin with a methylene chloride solution of monoethylsuccinyl chloride, at 25-28 degrees C for 3 hours in the presence of NaHCO3; 2. the transfer of the erythromycin ethylsuccinate from methylene chloride solution in acetone solution by distillation of mixture methylene chloride: acetone 1:1 at 25-28 degrees C; 3. erythromycin ethylsuccinate separation by crystallization in water at pH = 8-8.5 and 5 degrees C for 90 minutes. The quality control for the erythromycin ester was performed according to the Xth edition of Romanian Pharmacopoeia standards using national standard for erythromycin ethylsuccinate and national standard for erythromycin with an activity of 1: 937 U and 2.02% humidity. The Micrococcus luteus ATCC 9341 was used as a test microorganism and a thin layer cromatography was performed for qualitative control. RESULTS: 13.1 g of erythromycin ethylsuccinate were obtained with an output of the process of 82.02%. Using water for the separation of erythromycin ethylsuccinate the output of the process is greater (82.02%) than in case of using petroleum ether (74.14%) or hexane (80.25%). The thin layer cromatography revealed an Rf = 0.56 and the microbiological activity of the erythromycin ethylsuccinate was 98.7% compared with the standard. CONCLUSIONS: Using water instead of hexane or petroleum ether is gainful for the separation of erythromycin ethylsuccinate from the reaction medium. The obtained erythromycin ethylsuccinate corresponds to the Xth edition of Romanian Pharmacopoeia standards. So, the raw materials consumption is decreased, the costs are cut down, the obtained product purity is high and the output of the process is greater.

[Means of purification of cephalexin with a view to therapeutic use]. / Posibilitati de purificare a cefalexinei în scopul utilizarii terapeutice.

Cephalexin (CEX) is the generic word of chemical compound 7-(D-alpha-aminophenylacetamido)-3-methyl-3-cephem-4-carboxylic acid, which is part of first generation oral cephalosporins group. It is use as cephalexin monohydrochloride monohydrate (CEX.HCl.H2O) syrup or tablets for oral administration. For obtaining a compound with great solubility and osmotic pressure, which is ideal for pharmaceutical forms with controlled dosage, it is necessary to achieve the crystalline form of Cephalexin monohydrochloride monohydrate. The therapeutic use Cephalexin has an output over 95 %, so it is necessary to purify CEX depending on it's isoelectric pH (pKa), which is 4.2. A good purification took place at greater or less values of pH, then the isoelectric pH value of CEX. The purification of CEX at greater values of pH then isoelectric point, took place with a greater output (75-76%), and the obtaining Cephalexin is much pure (97-98%).