Cefoperazone also has a broad spectrum of antimicrobial action, including most clinically significant microorganisms: Gram-positive, Gram-negative, aerobic, and anaerobic. It is stable with respect to most beta-lactamases of Gram-positive and Gram-negative bacteria.
Cefoperazone is used for bacterial infections of the lower respiratory tract, urinary and sexual tracts, bones, joints, skin, soft tissues, abdominal, and gynecological infections. Synonyms of this drug are cefazon, cefobid, cefobis, and many others.
Moxalactam: Moxalactam, 7( [2-carboxy-2-(4-hydroxyphenyl)acetamido]-7 a-methoxy-3-(1-methyltetrazol-5-yl)-thiomethyl-1-oxa-dethia-3-cefem-4-carboxylic acid (18.104.22.168), is synthesized in a multi-stage synthesis from 6-APA, which is acylated by benzoylchloride in the presence of triethylamine to give 6-benzoylpenicillin (22.214.171.124). The carboxyl group of this compound is protected by a reaction with diphenyldiazomethane, to form the 3-diphenylmethyl ester of 6-benzoylpenicillin (126.96.36.199). Oxidation of this product with molecular chlorine under basic conditions gives the S-oxide of the 3-diphenylmethyl ester of 6-benzoylpenicillin (188.8.131.52). Upon reacting this with triphenylphosphine, the expected reduction of sulfoxide to sulfide does not occur, but rather the thiazine ring is opened, causing sulfur to be released while also resulting in its simultaneous substitution with oxygen and subsequent formation of a cyclic iminoester (184.108.40.206). Chlorinating the double bond of this product with chlorine and subsequent treatment of obtained dichloro derivative with sodium bicarbonate gives a chloromethyallyl derivative (220.127.116.11), which upon reaction with potassium iodide substitutes the chlorine with iodine, forming an iodomethylallyl derivative (18.104.22.168), and finally, hydrolyzing this product in dimethylsulfoxide in the presence of copper® oxide forms the corresponding allylic alcohol (22.214.171.124). Upon heating this in the presence of boron trifluoride-diethyl etherate, it recyclizes back to form an oxazine ring and the reverse transformation of the cyclic iminoester into the amide form (126.96.36.199). The exo-cyclic double bond of the resulting product undergoes chlorination and subsequent treatment of the product with a base using 1,7-diazabicyclo-[4.5.0]undec-6-ene (DBU), gives the
3-chloromethyl derivative (188.8.131.52). Reacting this with tert-butyl hypochlorite, obviously to make an N-chloro derivative, and then with lithium methoxide, after acidification and treatment with sodium thiosulfate gives diphenylmethyl ester of 7(-benzoylamido-7 a-methoxy-3-(chloromethylyl)-1-oxa-dethia-3-cefem-4-carboxylic acid (32.1.94). Reacting this with the sodium salt of 5-mercapto-1-methyl-tetrazol gives the diphenylmethyl ester of 7(-benzoylamido-7a-methoxy-3-(1-methyltetrazol-5-yl)-thiomethyl-1-oxa-dethia-3-cefem-
4-carboxylic acid (32.1.95). Debenzoylation of this product and subsequent treatment with phosphorous pentachloride in pyridine and then with methanol and diethylamine gives the diphenylmethyl ester of 7(-amino-7a-methoxy-3-(1-methyltetrazol-5-yl)-thiomethyl-1-oxa-dethia-3-cefem-4-carboxylic acid (184.108.40.206). Acylating this compound with the mixed anhydride synthesized from mono-diphenylmethyl ester of (4-hydroxyphenyl)malonic acid and oxalylchloride in the presence of triethylamine gives the bis-diphenylmethyl ester protection on both carboxyl groups of the desired product (220.127.116.11). Finally, removing the indicated protecting groups from both carboxyls by boiling it with trifluoroacetic acid in toluene gives the desired moxalactam (18.104.22.168) [168-173].
■'WS>cCH3 C6H5COC:/(C2H5)3^ G^C"N^^CH3 ^H^N, NHW-SN<cH3 CL,/0H
O COOH o' COOH O COOCH(C6H5)2
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