NOUVEAUX DERIVES ACYLES

摘要

1319018 Penicillins;α-benzoyloxy-alkanoic acids and intermediates F HOFFMANN-LA ROCHE & CO AG 16 July 1971 [17 July 1970] 33477/71 Heading C2A and C2C Novel penicillins having the general Formula (I) and salts and hydrated forms thereof, wherein X is hydrogen, halogen, NH2, NO 2 , CN, OH, CF 3 , C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, (C 1 -C 4 alkanoyloxy)-methyl, (C 1 -C 3 alkoxy)-methyl, (C 1 -C 3 alkoxy)-acetamido, hydroxy-(C 1 -C 3 alkyl), amino(C 1 -C 3 alkyl), di(C 1 -C 3 alkyl)amino, C 1 -C 3 alkylsulphonamido, C 1 -C 3 alkylsulphonyl, sulphamoyl, carbamoyl, phenyl or pyrrol-1-yl, or two Xs on adjacent carbon atoms together form a C 1 -C 3 alkylenedioxy group; n is 1, 2 or 3; and T is C 2 -C 5 alkyl or alkenyl, or cyclopropylmethyl or cyclobutylmethyl or an aralkyl group having up to 8 carbons, are prepared by condensing 6-aminopenicillanic acid having its carboxyl group protected, with an acid of general Formula (II) wherein X, n and T are as defined above and any strongly basic group X is protected, or a reactive functional derivative thereof, and cleaving off any protecting groups in the product. Pharmaceutical compositions having antibiotic activity against Gram-positive and Gramnegative bacteria comprise a penicillin of Formula (I) as defined above or a non-toxic salt thereof together with a compatible pharmaceutical carrier. Aroyloxyalkyl carboxylic acids having the Formula (II) as defined above are prepared by either (a) reacting an optically active or racemic acid of Formula (III) or a readily-cleavable ester thereof, with a reactive acid derivative (e.g. anhydride or halide) of a compound of Formula (IV) in the ease of the ester of (III) the reaction being conducted in the presence of a base (e.g. NaHCO 3 , pyridine or triethylamine), and then when necessary cleaving off the ester group; or (b) reacting a readily-cleavable ester of an optically active or racemic compound of Formula (V) wherein Y is halogen, with an alkali metal or alkaline earth metal salt of a compound (IV) or the compound (IV) in the presence of a tert. nitrogenous base and then cleaving off the ester group. Typical readily-cleavable esters are benzyl ester and tert. butyl ester.