Improvements in or relating to penicillin derivatives

摘要

The invention relates to penicillins of the general formula where X is an amino-substituted acyl group containing up to 20 carbon atoms and having the formula where R is hydrogen or an amino, carboxyl or substituted or unsubstituted alkyl, aryl, aralkyl or heterocyclic group, and n is zero or an integer, and non-toxic salts thereof. X may be where n is zero or 1 to 6, and R is hydrogen or an alkyl, aryl, aralkyl or heterocyclic group which may be substituted; R being phenyl, chlorophenyl, methoxyphenyl, furyl or cyclohexyl when n is zero where n is 1 to 4. Typical penicillins are a -aminobenzyl penicillin, a -amino-p-methoxybenzyl penicillin, a -amino-2-furylpenicillin, a -aminoheptylpenicillin, a -aminopentyl penicillin, a -aminocyclohexyl penicillin and a -amino-p-chlorobenzyl penicillin. The non-toxic salts are, e.g. the sodium, potassium, calcium, aluminium, ammonium and substituted ammonium salts, e.g. salts of trialkylamines, procaine, dibenzylamine, N-benzyl-beta-phenylethylamine, 1-ephenamine, N,N1-dibenzylethylene diamine, dehydroabietylamine and N,N1-bis-dehydroabietylethylene diamine. The penicillins are produced by reacting 6-aminopenicillinic acid with an acid of general formula XOH (where X is as defined above) having its amino group or groups protected, or a salt thereof, and thereafter removing the protecting group or groups under sufficiently mild conditions to avoid destruction of the penicillin nucleus. The acid may be in the form of a mixed anhydride prepared by reacting the amino-substituted carboxylic acid, or a salt thereof, having its amino groups protected, with an ester of chlorocarbonic acid. The protecting group may be a trityl group or a group of general formula R11O.CO- where R11 is an alkyl, benzyl, substituted benzyl, phenyl or substituted phenyl group. The protecting groups may be removed by catalytic hydrogenation using palladium on a barium carbonate support. Specifications 870,395 and 870,396 are referred to.