SYNTHETIC PENICILLINS

摘要

1289358 Penicillins; antibacterial compositions TAKEDA YAKUHIN KOGYO KK 24 Sept 1969 [28 Sept 1968] 46937/69 Heading C2A Penicillins of the general formula wherein R 1 and R 2 are the same or different and each represents hydrogen, C 2-12 alkyl, aralkyl or a mono- or poly-substituted or unsubstituted phenyl, pyridyl, naphthyl or thienyl, the substituents being nitro, sulpho, carboxyl, halo, C 1-6 alkyl or C 1-6 alkoxy and, in the case of polysubstitution being the same or different, or alternatively, R 1 and R 2 together represent a polymethylene group of 4 to 6 carbon atoms, and pharmaceutically acceptable salts or acid salts thereof, are prepared by reacting 6-aminopenicillanic acid in free or salt form or a silyl derivative thereof with an acylating agent derived from anα-sulphocarboxylic acid having the general formula and, if desired, converting the penicillin compound by treatment with a base to a pharmaceutically acceptable salt or acid salt thereof such as Na, K, Mg, Ca, or Al salts or salts formed with ammonia, triethylamine, procaine or dibenzylamine. Theα-sulphocarboxylic acid may be in the form of its halide, acid anhydride, azide, ester, thioester, azolide or theα-sulphocarboxylic acid may be coupled with an N,N- carbonyl ditriazole, a carbodiimido, a ketenimine or an isoxazolium salt. The optically active D isomers of the above penicillins containing an asymmetrical carbon atom may be prepared by (1) reacting 6-aminopenicillanic acid or its silylated derivative with an acylating agent derived from the optically active D isomer of a suitableα-sulphocarboxylic acid or (2) reacting 6-amino-penicillanic acid or its silylated derivative with an acylating agent derived from a suitable racemicα-sulphocarboxylic acid to produce a racemic penicillin and subsequently recovering the optically active D isomer of the penicillin by means of chromatography or recrystallization. Antibacterial compositions having activity against Gram-positive and Gram-negative bacteria comprise the above penicillins of Formula I. The compositions may be administered orally or parenterally in the form of capsules, tablets, solutions or suspensions.