GB1212551A - Penicillins - Google Patents

Abstract

1,212,551. Penicillins. ANKERFARM S.p.A. 8 March, 1968 [8 March, 1967], No. 11530/68. Heading C2A. A semi-synthetic penicillin is produced by the acylatiqn of 6 - aminopenicillanic acid adsorbed on an anion exchange resin e.g. Amberlite (Registered Trade Mark) IRA-401. The 6-APA is obtained by the enzymatic hydrolysis of a penicillin such as benzyl penicillin. Preferably the penicillin acylase is derived from a micro-organism resistant to high concentrations of the acyl moiety of the starting penicillin, e.g. phenylacetic acid or phenoxyacetic acid. Thus, in the case of benzylpenicillin, the micro-organism may be a mutant of E. coli Ankerfarm Sp. 27/14 (CBS 128À67) cultured serially on media containing increasing concentrations of phenylacetic acid or phenoxyacetic acid. The hydrolysis of the penicillin may be carried out with cultures or enzyme extracts of the micro-organisms. After hydrolysis, impurities may be removed by extraction with a water-immiscible solvent, e.g. ether, and the aqueous phase containing the 6- APA treated with the resin at pH 6À0. The 6-APA resinate is separated from the solvent, washed to remove impurities and then suspended in water of pH 7 to 9 containing sodium chloride. The acylating agent is used as the chloride or anhydride, which is dissolved in a watermiscible solvent such as acetone and added to the aqueous suspension of 6-APA resinate at e.g. 0‹ C. After acidifying to e.g. pH 2À0, the result ant penicillin may be extracted with a waterimmiscible solvent e.g. ethyl acetate. The penicillin may be recovered as a salt by extracting the organic solution thereof with an aqueous solution of a base, e.g. sodium bicarbonate solution.