| 摘要 |
1,245,586. Fluorophenylacetamidopenicillanic acids. ASTRA AB. 20 March, 1969 [22 March, 1968], No. 14055/68. Headings C2A and C2C. Novel 6 - [α - (fluorophenyl) - α - azidoacetamido] penicillanic acid, of Formula (I) or non-toxic salts thereof are prepared by reacting an acylating derivative of an α-azido-o-, m- or p-fluorophenylacetic acid, or. the acid itself in the presence of a condensing agent, with a 6-aminopenicillanic acid or a reactive derivative thereof, optionally in the form of a salt or easily hydrolysed ester, and if necessary hydrolysing the ester. The acylating derivative may be the acid chloride, bromide, azide, activated ester or anhydride, or activated heterocyclic amide. 6-APA derivatives are preferably di- or tri- (C 1 -C 6 alkyl) silyl derivatives; the esterifying group may be a similar silyl radical or a trialkyl or triaryltin group. The reaction is carried out in aqueous, organic or aqueous-organic medium, preferably in the presence of an acid-binding agent. By using the appropriate optical isomer of the acylating acid, the corresponding + and - isomers of the products are prepared. α-Azido-o-, m- and p-fluorophenylacetic acids are prepared by reacting the corresponding α- bromo-acid with sodium azide. The products are resolved into their + and - forms by fractional crystallization of a suitable salt (e.g. ephedrine, pseudo-ephedrine or amphetamine salt). The acids are converted to their chlorides by treatment with thionyl chloride. Pharmaceutical compositions having antibiotic activity comprise 6-[α-(fluorophenyl)-α-azidoacetamido] penicillanic acids of Formula I or a non-toxic salt thereof together with a pharmaceutically acceptable carrier or diluent. Reference has been directed by the Comptroller to Specifications 1,008,468 and 964,449. |
