Transformations of penicillin. Part 8. Preparation of 2-acetylceph-3-em derivatives from carboxy-protected penicillin S-oxides

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Abstract
Carboxylic acids were protected by formation of acylhydrazine or acylhydrazone derivatives. The influence of N-substitution on the ease of carboxylic acid regeneration by oxidation under mild conditions is described. Such hydrazine derivatives have been applied in protecting the 3- and 4-carboxy-functions of substituted penicillins and deacetoxycephalosporins. Pencillin G S-oxide, protected as the N′-diphenylmethylene-N-methylhydrazide, was converted into the novel 2-acetyldeacetoxycephalosporin G. The sulphenic acid from pyrolysis of the protected penicillin S-oxide was trapped with n-propyl isopropenyl ether to give the 1,2-secopenicillin enol ether derivative. Mercury(II)-nitrate-catalysed hydrolysis gave the corresponding 4-(acetylmethylthio)azetidin-2-one. Ozonolysis of the azetidinone isopropenyl function gave the derived diketone. This on 1,5-diazabicyclo-[4.3.0]non-5-ene-catalysed cyclisation and subsequent dehydration gave the novel protected 2-acetyldeacetoxycephalosporin G. The protection of carboxylic acids via formation of dihydro-heteroaromatic amides is described. Mild oxidation of these derivatives gave the corresponding heteroaromatic amides, which were readily hydrolysed, regenerating the carboxylic acids. Attention is directed to the use of fluoride anion as a base in penicillin and cephalosporin chemistry.

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