GB1176501A - Leucomycins A3 to A9 - Google Patents

Abstract

1,176,501. Leucomycins A3 to A9. KITASATO INSTITUTE and TOYO JOZO K.K. 1 Sept., 1967 [5 Sept., 1966 (4); 21 Sept., 1966 (2); 25 Feb., 1967 (2)], No. 40046/67. Heading C2A. Leuconycin components A 3 to A 9 are produced by cultivating a leucomycin-producing strain of streptomyces kitasatoensis e.g. NRRL 2486 and 2487 in an aqueous nutrient medium. The crude leucomycin is extracted from the clarified broth at pH 7À5 to 9 with a waterimmiscible organic solvent such as benzene or butyl acetate, treated with an aqueous acid (e.g. aqueous hydrochloric acid) of pH 2 to 4 and re-extracted with a water-immiscible organic solvent (e.g. benzene) at pH 7À5 to 9À0. The extract is concentrated and crude leucomycin recovered by (a) addition of petroleum ether, (b) pyophilization or (c) adjustment to pH 7À0 to 9À0. The leucomycin components A 3 to A 9 are separated by (a) chromatographic adsorption on silica gel or activated alumina and developed with benzene/acetone or benzene/methanol solvent systems, and (b) countercurrent distribution using benzene/chloroform/ methanol/citric acid buffer of pH 4À9 (20 : 6 : 20 : 8). The mixture of leucomycin antibiotics A 3 to A 9 is a white powder; mpt. 128-145‹ C., containing C = 60À00%, H = 8À80%, N = 1À68%; U.V. spectrum max. at 231 mÁ with 1% E = 353; mol. wt. 800, α] D <SP>25</SP> = - 53 degrees 1cm. (1% in chloroform); soluble in methanol, ethanol, ethyl acetate, butyl acetate, acetone, methyl ethyl ketone, benzene and chloroform; difficulty soluble in water; insoluble in petroleum ether. The antibiotics form salts with acids. They have the formula wherein R 1 is hydrogen and R 2 is acetyl (A9) or propionyl (A7) or butyryl (A5); or wherein R 1 is acetyl and R 2 is acetyl (A8) or propionyl (A6) or butyryl (A4) or isovaleryl (A3).