CEPHALOSPORIN COMPOUNS

摘要

1,241,655. N-Deacylating cephalosporin compounds. GLAXO LABORATORIES Ltd. 6 Aug., 1968 [21 Aug., 1967], No. 38492/67. Heading C2A. 7# - Acylamino - 4 - carboxy - cephalosporin compounds (other than those having at position- 7 a #-aminoadipoylamino group which are optionally blocked at the amino and/or carboxy groups) are N-deacylated by reacting with an imide-halide-forming reagent, converting the resulting imide halide into an imino ether and hydrolysing or alcoholysing the latter to give a 7#-amino-cephalosporin compound. The 4- carboxyl group of the starting material is preferably blocked, e.g. by esterification with an easily removable esterifying group such as a diphenylmethyl, t-butyl, #,#,#-trichloroethyl or silyl group. Any other functional groups which may be present are blocked if necessary. Typical 7#-acyl groups which may be removed are thienylacetyl, phenylacetyl, phenoxyacetyl, benzoyl and acetyl. The starting materials may have at the 3-position a methyl, hydroxymethyl, etherified hydroxymethyl, or acyloxymethyl group or a group derived from a nucleophile. Suitable imide-halide-forming agents are acid halides of phosphorus acids, e.g. phosphorus oxychloride or pentachloride. The reaction is preferably effected in an inert organic solvent in the presence of a base such as triethylamine, pyridine, dimethylaniline or calcium carbonate. Conversion to the imino ether is preferably by reacting with an alcohol, e.g. methanol, in the presence of a tertiary amine such as listed above. The imino-ether may be decomposed with water or an alkanol in the presence of an acidic or basic catalyst, e.g. hydrochloric, trifluoroacetic, toluenesulphonic, phosphoric or formic acids, or ammonia or salts of a weak acid with alkali- or alkaline earth-metals. The N-deacylated products are useful as intermediates for re-acylation by a different 7#-acylating group to give antibiotically active cephalosporin compounds.