GB1364521A - Aminoglycoside antibiotics - Google Patents

Abstract

1364521 Substituted gentamicins MERCK & CO Ine 2 June 1972 [16 July 1971] 33583/71 Heading C2A The invention comprises substitution products of gentamicin C 1 , gentamicin C 1a or gentamicin C 2 having a substituent on the C-2 carbon of ring Sc chosen from -OR 1 , =O, -OH, -OSO 2 CH 3 , and -NH 2 , wherein R 1 is C 1 -C 6 alkyl, R is hydrogen, C 1 -C 6 alkyl, or C 2 -C 6 alkenyl; wherein the hydroxy and methanesulphonyloxy have the episteric position; and wherein the amino substituent can be either in normal or epi-steric position. Gentamicin has the Formula I wherein in gentamicin C 1 R=R<SP>1</SP>=CH 3 ; in gentamicin C 2 , R = CH 3 and R<SP>1</SP> = H; and in gentamicin C 1a , R=R<SP>1</SP>=H. The invention also comprises substitution products of gentamicin C 1 , gentamicin C 1a or gentamicin C 2 having a substituent on the C-5<SP>1</SP> carbon of ring S b chosen from C 1 -C 6 alkoxy, carbamoyl, C 1 -C 6 alkylcarbamoyl, C 2 -C 6 alkenyl, carbamoyl and methanesulphonyl; or having two carbamoyl substituents on both the C-2 carbon of ring S c and the C-5<SP>1</SP> carbon of ring S b . The various substitution products are prepared by treating the penta-N-blocked gentamicin having the desired C-2, C-5<SP>1</SP> or di C-2, C-5<SP>1</SP> substituent(s) under conditions to remove the blocking agent. The blocking groups may be carbobenzoxy or acetyl. The carbobenzoxy blocking group may be removed using hydrogen over a 10% palladium/carbon catalyst. The acetyl group may be removed by alkaline hydrolysis, e.g. by use of a catalytic amount of sodium methoxide in methanol or by the use of barium hydroxide. A pharmaceutical composition contains, as active ingredient at least one gentamicin substitution product described above or a salt thereof together with a pharmaceutically acceptable diluent or carrier.