GB1259682A - Josamycin derivatives - Google Patents

Abstract

1,259,682. Acyl derivatives of the antibiotic Josamycin. YAMANOUCHI PHARMACEUTICAL CO. Ltd. 25 March, 1969 [29 March, 1968 (2)], No. 15654/69. Heading C2A. Novel acyl derivatives of the antibiotic Josamycin, wherein one or both of the secondary hydroxyl groups are acylated, are prepared by treating the antibiotic with a carboxylic acid or an acylating derivative thereof (e.g. the anhydride or halide), (a) using one equivalent of acylating agent to give acyl-josamycin-1; or (b) using two or more equivalents of the agent under basic reaction conditions to give diacyljosamycin; and optionally (c) hydrolysing diacyl-josamycin to give acyl-josamycin-2. The acyl derivatives 1 and 2 differ in the position of - the acylated hydroxyl group, as shown by the respective melting points of the acetyl derivatives, 182-183‹ C. and 128-131‹ C. The acylating groups may be acetyl, propionyl, butyryl, benzoyl, or isovaleroyl. Reaction (a) is preferably carried out in an organic solvent (e.g. lower alcohols, ethyl acetate or acetone) with heating; an acid acceptor, e.g. NaHCO 3 , may be present when the acid halide is used as the acylating agent. The di-acylation (b) is preferably carried out using the acylating acid anhydride as a reaction medium, with the addition of an organic base such as pyridine or quinoline. Hydrolysis (c) may be effected by heating the diacyl product in aqueous-alcohol, -acetone, -methylethylketone, -dioxane or -dimethylformamide, preferably with the addition of an inorganic base or acid. If the products do not crystallize out spontaneously from the reaction mixture, they may be recovered by adding a non-solvent and/or concentrating the mixture. The acyl derivatives lack the bitter taste of josamycin while retaining its antibiotic activity. Pharmaceutical compositions comprise a mono- or di-acyl derivative of the antibiotic josamycin together with an acceptable carrier; they are in forms for oral administration, such as tablets, powders, granules, syrups, chewable tablets or capsules.