IMPROVEMENTS IN OR RELATING TO CEPHALOSPORIN COMPOUNDS

摘要

1,241,658. 3-Substituted cephalosporin derivatives. GLAXO LABORATORIES Ltd. 6 Aug., 1968 [21 Aug., 1967], No. 7715/71. Divided out of 1,241,657. Heading C2A. Novel 7-amino and 7#-acylamino-cephalosporanic acids and derivatives (e.g. salts, esters or anhydrides) thereof, having a group -CH 2 P at the 3-position in which P is a Cl, Br or I atom or a formyloxy, isothiocyanato or haloacetoxy group, are prepared by (a) reacting the corresponding 3-CH 2 OH compound with thionyl chloride or bromide or an acid chloride or bromide (e.g. N,N-dialkyl- or N,N-diarylchloro- or bromo-sulphinamide) to give the 3-CH 2 Cl and 3-CH 2 Br derivatives respectively; (b) reacting the corresponding 3-CH 2 OH compound with phosphorus tribromide and pyridine to give the 3-CH 2 Br derivative; (c) reacting the 3-CH 2 Cl or 3-CH 2 Br derivative with alkali metal iodide to give the 3-CH 2 I derivative; (d) acylating the 3-CH 2 OH compound with a haloacetyl or formyl halide to give derivatives wherein P is haloacetoxy or formyloxy; and (e) reacting the 3-dichloroacetoxymethyl compound with potassium thiocyanate to give the derivative in which P is isothiocyanato. The reactions are preferably performed using cephalosporanic acids having a protected carboxylic group at position -4, e.g. esters thereof such as the diphenylmethyl; #,#,#- trichloroethyl or t.-butyl esters, such protecting groups being subsequently removed, if desired, by conventional methods. The preferred 7#- acylating groups are 21-thienylacetyl, phenylacetyl or phenoxyacetyl. The inventive compounds are useful as intermediates for reaction with nucleophilic reagents to prepare 3-nucleophilic group-substituted cephalosporin antibiotics.