The antibiotic a22765 and salts thereof

摘要

The antibiotic A22765 or an acid addition salt thereof is prepared by growing Streptomyces aureofaciens NRRL 2858 or another antibiotic A22765-producing strain of S. aureofaciens or an antibiotic A22765-producing mutant of either strain under aerobic, preferably submerged aerobic, conditions in an aqueous nutrient solution containing an assimilable carbon source, a nitrogenous compound and an inorganic salt until the culture displays a substantial antibiotic action, and the antibiotic A22765 or an acid addition salt thereof is then isolated from the nutrient solution and, if desired, the basic antibiotic is treated with an acid to form an acid addition salt thereof. Cultivation is preferably carried out at 18-40 DEG C. for 26-120 hrs. The antibiotic A22765 is extracted from the culture filtrate and the mycelium washings preferably at pH 4-6 by one of the following procedures: (i) adsorbtion on active carbon, an activated earth or a resin adsorber and elution with a mixture of water-miscible organic solvent with water or an aqueous acid, (ii) adsorbtion on an ion exchange resin containing free carboxylic or sulphonic acid groups and elution with dilute acid, (3) precipitation with picric acid. The precipitate may be treated with a salt of an organic base or with aldiute acid to form the corresponding salt, (4) treating an aqueous or alcoholic aqueous solution of the salt with an excess of an organic water-miscible solvent, (5) extracting with a solution of phenol in chloroform, while varying the pH of the aqueous solution and the phenol content of the chloroform solution. The antibiotic may be purified by methods (5) or (6) and in addition adsorbtion chromatography on an adsorbent or an ion exchange resin containing carboxylic or sulphonic groups, partition chromatography or counter-current distribution. The antibiotic A22765 has the following properties, elemental analysis C=49.8%, H=7.6%, N=10.2%, Fe=2.4% and O=30.0%; the acetate decomposes at 165 DEG C. without melting; it is a pale brown powder soluble in water, methanol, dimethyl formamide and phenol; it has a U.V. spectrum as shown in Fig. 2; on Whatman paper No. 1 in N/3 acetic acid the antibiotic migrates at 220 volts and 1.7 ma. in 3 hrs. a distance of 4.5 cm towards the cathode to fructose; it has an I.R. spectrum as shown in Fig. 1 and is basic and forms salts with many acids typical examples of which are hydrochloric, sulphuric, propionic, oleic, succinic and pantothenic acid. The salts are formed by direct action of the acid or double decomposition of salts. The free base is obtained from the sulphate by treatment with aqueous barium hydroxide, neutralisation of excess baryta with CO2, separating the precipitated sulphate and carbonate and isolating the free base by freeze drying; or by use of a strongly basic anion exchanger. The antibiotic A22765 or its salts may be used in pharmaceutical preparations for oral, parenteral or local administration in the form of tablets, dragees, powders, ointments, creams, suppositories, solutions, suspensions or emulsions. Specification 963,904 is referred to.