GB899199A - Production of ª--substituted alkyl penicillins and salts thereof - Google Patents

Abstract

The invention relates to a -substituted alkyl penicillins and salts thereof of general formula <FORM:0899199/IV (b)/1> in which R is hydrogen, alkyl, alkoxyl, amino, nitro, cyano, hydroxyl or halogen, R1 is alkyl, R2 is hydrogen or a non-toxic salt-forming radical and X is oxygen or sulphur. Specified salts are sodium, potassium, ammonium and substituted ammonium, e.g. procaine, dibenzylamine, N,N1-dibenzylethylenediamine, N-benzyl-beta-phenethylamine and 2-methylamino-1,2-diphenyl ethanol (l-ephenamine). The compounds are produced by reacting 6-aminopenicillanic acid or a salt thereof, with an a -substituted alkanoic acid or functional derivative thereof containing the group <FORM:0899199/IV (b)/2> wherein R, R1 and X have the above values, and then if R2 of formula 1 is hydrogen, if desired, reacting the product with a base having a non-toxic salt forming radical. The a -substituted alkanoic acid reactant may be (a) the a -substituted alkanoic acid together with a 1,3-substituted carbodiimide, e.g. 1,3-dicyclohexylcarbodiimide (b) an alkanoyl chloride, e.g. a -phenoxypropionyl chloride (c) an acid anhydride, e.g. a -phenoxypropionyl anhydride or (d) a mixed acid anhydride, e.g. t-butoxy-formic a -phenoxypropionic anhydride produced in situ from t-butyl chlorocarbonate and a -phenoxypropionic acid. Examples relate inter alia to the preparation of the potassium, sodium, procaine and N,N-dibenzylethylenediamine salts of a -phenoxyethylpenicillin; the potassium and procaine salts of a -phenylmercapto-ethyl penicillin; and the potassium salt of a -phenoxy-b -methyl propyl penicillin.