GB1377573A - Acrloxyalkyl ester derivatives of penicillin and cephalosporin - Google Patents

Abstract

1377573 Penicillin and cephalosporin esters YAMANOUCHI PHARMACEUTICAL CO Ltd 5 April 1972 [5 April 1971 19 April 1971 20 April 1971 11 Aug 1971] 15715/72 Heading C2C Novel acyloxyalkyl esters of ampicillin, cephaloglycin and cephalexin having the general Formula (I) wherein A is a group of formula in which R<SP>1</SP> and R<SP>2</SP> each represents an unsubstituted or substituted alkyl, cycloalkyl, alkenyl or phenyl group wherein the substituent is a phenyl group, a phenoxy group or a halogen atom or atoms, and R<SP>3</SP> is a hydrogen atom or an acetoxy group, and acid addition salts of the said esters, are prepared by esterifying 6-aminopenicillanic acid, 7-aminocephalosporanic acid or 7-aminodesacetoxy-cephalosporanic acid, or an N-acylated derivative of these compounds, by reacting the alkali metal salt thereof with an acyloxyalkyl halide of formula wherein R<SP>1</SP> and R<SP>2</SP> are as defined above and X is a halogen atom. The resulting ester is then N-acylated by reaction with an acylating derivative of phenylglycine (e.g. the acid chloride hydrochloride) to give the desired compound (I) or, if an N-acylated starting compound was used, the product is reacted with phosphorus halide in the presence of a tertiary amine to give an imide halide, converted to an imino-ether by reaction with an alkanol and the imino-ether is reacted with phenylglycine or an acylating derivative thereof, followed by hydrolysis with water or an alkanol to give the compound (I). Alternatively the acyloxyalkyl ester of a penicillin may be oxidized to the S-oxide which is heated in the presence of an acid to effect ring expansion to the corresponding ester of desacetoxycephalosporanic acid. The latter is then treated with phosphorus halide, an alkanol and then with phenylglycine as described above to give the required N-acyl group of the compound (I).