GB1418399A - Antibiotic derivatives - Google Patents

Abstract

1418399 Tobramycin derivatives BRISTOL-MYERS CO 8 March 1973 [8 March 1972] 11296/73 Heading C2C Novel antibiotic tobramycin derivatives having the general Formula (IV): and acid addition salts thereof, wherein R<SP>2</SP> is L - (-) - γ - amino - α - hydroxybutyryl, L - (-)- # - amino - α - hydroxypropionyl or L - (-) - #- amino-a-hydroxyvaleryl, are prepared by the consecutive steps of (a) treating tobramycin with an acylating agent selected from compounds having the following formulae: wherein R<SP>4</SP> and R<SP>5</SP> are alike or different and each is H, F, Cl, Br, NO 2 , OH, C 1-6 alkyl or C 1-6 alkoxy, and X is Cl, Br or I, or with a functional N-acylating equivalent of such a compound, in a proportion of up to 1 mole of said agent per mole of tobramycin, to produce an intermediate compound of Formula (II): wherein Y is a group of formula: and R<SP>4</SP> and R<SP>5</SP> are as defined above; (b) acylating the compound (II) with an acylating agent of Formula (VII) in which n is 1, 2 or 3, W is a group of one of the formulae ascribed to Y above, and M is a group of formula or with an N-acylating functional equivalent of such a compound, in a proportion of at least 0À5 mole of said agent per mole of compound (II), to produce a compound of Formula (III): wherein n, y and w are as defined above; and (c) removing the blocking groups y and w, and if desired converting the product (IV) into an acid addition salt, (e.g. the sulphate and disulphate). The inventive compounds (IV) and their non- toxic acid addition salts have antibiotic activity, and may be admixed with pharmaceutically acceptable diluents or carriers to provide antibiotic pharmaceutical compositions.