2-ACYLOXYCEPHALOSPORIN COMPOUNDS HAVING ANTIBIOTIC ACTIVITY,INTERMEDIATES USEFUL IN THEIR PREPARATION AND PROCESS FOR PREPARING SAID COMPOUNDS AND INTERMEDIATES

摘要

1,269,147. 2-Acyloxy cephalosporins. ELI LILLY & CO. 6 Oct., 1969 [7 Oct., 1968], No. 49068/69. Heading C2A. Novel 2 - acyloxy - 7 - (protected amino) cephalosporins having the formula wherein R is a protected amino group; R2 is methyl, in which R5 is H, C 1 to C 6 alkyl, C 5 to C 7 cycloalkyl, or a radical of formula where Y is F, Cl, Br, C 1 to C 3 alkoxy, -NO 2 , or -CF 3 , m = 0 or 1, and s is 0, 1, or 2; R3 is C 2 to C 8 alkanoyloxy or C 6 to C 8 cycloalkanoyloxy; and R4 is H or a residue of an esterifying alcohol, are prepared by reacting a protected 7-amino cephalosporin ester of formula wherein R1 is a residue of an esterifying alcohol and R and R2 are as above, with a lead tetraacylate of formula Pb(R3) 4 , R3 being as above and if required converting the ester group R1 to hydrogen. The novel compounds may have antibiotic activity, or if not, provide intermediates for preparing cephalosporin antibiotics, e.g. by removing the N-protecting group and reacylating, or replacing the R2 group by other groups by conversion to the 3-(bromomethyl) derivative followed by reaction with a suitable nucleophilic compound. The preparative reaction is preferably carried out in a solvent, e.g. ethers, tertiary amides and alcohols, or hexamethylphosphoramide. Typical N-protecting groups include tritylamino, (trimethylsilyl)amino, acylamido and phthalimido. The ester group R1 may be removed by treating with Zn and CH 3 .COOH, or with trifluoracetic acid, or by hydrogenation using palladium black.