Cephamycinic acid, 7-amino

Cefminox. [6R-[6a,7thio]methyl]S-oxo-S-thia-I-azabicyc (o-[4.2.0]oct-2-ene-2-carboxytic add 7,5-t2-1 -amino -2-ea rb-oxyethy]thioacetamido)-7 -methoxy-3-[[(l -methyl-12f-tetrazol 5-yl)thio]methyl]-3-cephem -4 -carboxylic acid. C)6HnN707S3 mol wt 519.57. C 36.99%, H 4.07%, N 18.87%, O 21.56%, S 18.51 %. Semisynthetic broad spectrum cephamycin antibiotic. Prepn Belg. pat. 880,686, K. 

As for the cephalosporins, one of the first areas of cephamycin chemistry to be investigated concerned the replacement of the amidoadipic side chain with new acylamino substituents. This was first achieved by a novel acyl exchange reaction (176,177). Under appropriate conditions the cephamycin C ester (204) can be converted to diacyl derivatives such as (205). Removal of the trichloroethyl protecting groups leads to formation of the piperidone (206) and the new cephamycin ester (207). Deprotection of the latter affords the important semi-synthetic derivative cefoxitin. Other routes making use of the chemistry of various derived imines and imidoyl chlorides have been described (178—181). Another approach makes use of the reaction of (204) with oxalyl chloride to give the oxamic acid (208) with diphenylcarbodiimide (208) produced the amino ester (209) and the trione (210) (182). 

The cephalosporin produced by Streptomyces clavuligerus, cephamycin C (203), has also been shown to be derived from the amino acids a-aminoadipic acid, cysteine and valine 288), DL-[1- C]-Cysteine, DL-[3- C]-cysteine, DL-[l- " C]-valine and DL-a-amino-[l- C]-adipic acid all labelled cephamycin C. Acid hydrolysis of cephamycin C, followed by separation of the hydrolysis mixture using an amino acid analyser, indicated that DL-a-amino-[l- C]-adipic acid was specifically incorporated into the acylamino side chain. The 7-methoxy group was shown to be derived from L-[me//i> /- C]-methionine. 

The only natural derivatives of a-hydroxy-a-amino acids found to date are the 7-methoxycephalosporins (1) (cephamycins) (271), an important class of therapeutically valuable antibiotics. 

The most important a-alkoxy-a-amino acid compounds are the cephamycins (7-methoxycephalosporins) (1) (5, 271), which are of considerable therapeutic significance by virtue of their activity against Gram negative bacteria. Several methods have been developed for the conversion of penicillins and cephalosporins into their 6-(7-)methoxy derivative (44). 

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