This drug has a broad spectrum of antimicrobial action that includes the majority of the clinically significant microorganisms: Gram-positive, Gram-negative, aerobic, anaerobic, and blue-pus bacillus. It is resistant with respect to most beta-lactamases of Gram-positive and Gram-negative bacteria.
It is used for peritonitis, sepsis, meningitis, cholangitis, empyema of the gall bladder, pneumonia, lung abscesses, pyelonephritis, infections of the bones, joints, skin, soft tissues, abdominal and gynecological infections, and for infected wounds and burns. The main synonym of this drug is rocefin.
Ceftazidime: Ceftazidime is 1-[[7-[[(2-amino-4-thiazolyl)[(1-carboxy-1-methylethoxy) imino]acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]pyridin-2-carboxylic acid (126.96.36.199). As is the case in synthesis of ceftriazone, the synthesis of ceftazidime requires the preliminary synthesis of two starting compounds. 7-Amino-3-(1-pyridinomethyl)cef-3-en-carboxylic acid dihydrochloride is used as the cephalosporin fragment, while the acyl fragment is a modified structure of (188.8.131.52), which is not a derivative of 2-(2-amino-4-thiazolyl)-2-methoxyminoacetic acid, but a derivative of 2-(2-amino-4-thiazolyl)-2-(2-tert-butoxycarboxyl-2-propylox-imino)acetic acid, which is synthesized by the following scheme. Nitration of ace-toacetic ester gives isonitrosoacetoacetic ester (184.108.40.206), which undergoes chlorination by sulfuryl chloride in methylene chloride to form 4-chloro-2-hydroximinoacetoacetic ester (220.127.116.11).
Reacting this with thiourea in the classic scheme of thiazole synthesis by reacting of a-halogencarbonyl compounds with thioamides forms the ethyl ester of (Z )-2-(2-aminoth-iazole-4-yl)-2-hydroxyminoacetic acid (18.104.22.168). The amino group in this molecule is protected by a reaction with triphenylchloromethane in dimethylformamide in the presence of triethylamine, which gives the ethyl ester of (Z)-2-(2-tritylaminothiazole-4-yl)-
2-hydroxyminoacetic acid (22.214.171.124). The hydroxyl group in the resulting compound is alkylated with the tert-butyl ester of a-bromoisobutyric acid in dimethylsulfoxide in the presence of potassium carbonate, giving ethyl ester of 4-thiazoleacetic acid, a-[[2-(1,1-dimethylethoxy)-1,1-dimethyl-2-oxoethoxy]imino]-2-[(triphenylmethyl)amino], (Z) (126.96.36.199). The ethoxycarbonyl group in this molecule is hydrolyzed by sodium hydroxide, and upon working up the reaction mixture with an acid, the corresponding acid (188.8.131.52) is isolated (184.108.40.206). Upon interaction with phosphorous pentachloride the acid chloride (220.127.116.11) is obtained, which is used further as the acylating reagent.
The second necessary fragment, 7-amino-3-(1-pyridinomethyl)cef-3-en-carbonic acid (18.104.22.168), is synthesized from cefalosporidin (22.214.171.124), a cephalosporin antibiotic that is used independently in medicine and which is synthesized in the form of an internal salt by reacting cefalotin (126.96.36.199) with pyridine to replace the acetoxyl group with a pyridine group. Initially treating cephaloridin with trimethylchlorosilane in the presence of dimethylaniline and then with phosphorous pentachloride, followed by a reaction with 1,
3-butandiol results in the creation of 7-amino-3-(1-pyridinomethyl)cef-3-en-carboxylic acid (188.8.131.52). This is acylated by the acid chloride (184.108.40.206) synthesized earlier, forming the product (220.127.116.11), which is treated with a mixture of formic and hydrochloric acids to remove both protective groups (triphenylmethyl and tert-butyl), giving cef-tazidime (18.104.22.168) in the form of a dihydrochloride [157-162].
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