GB768007A - A new antibiotic cycloserine and method of preparing the same - Google Patents

Abstract

<PICT:0768007/IV(b)/1> A new antibiotic, cycloserine, is produced by cultivating Streptomyces orchidaceus (described) NRRL-2454 in an aqueous nutrient medium under submerged aerobic conditions at a temperature of 20 DEG to 30 DEG C., and preferably 20 DEG C., for 1 to 5 days. The medium contains (a) a source of carbohydrate such as glucose (preferred), sucrose, lactose, maltose, starch and glycerol; (b) a source of nitrogen, e.g. soybean products (preferred), alfalfa meal, amino acid cake, milk solids, whey nutrient, dried wheat slop, ground wheat, casein, a bone albumenoid material and enzymalic digest of lactalbumia; (c) calcium carbonate; (d) antifoaming agent. Cycloserine is recovered from the clarified broth by adsorption on (a) strongly basic anion exchange resins, e.g. "Amberlites" (Registered Trade Mark) IRA-400 and IRA-410 and Dowex-2 and elution with anions other than OH, e.g. chloride, sulphate, acetate and formate; (b) strongly acid cation exchange resins, e.g. Amberlite IR-120. The elute is decolorized with carbon and the cycloserine precipitated as the silver salt by the addition of a soluble silver salt, e.g. silver nitrate. The silver cycloserine is decomposed with aqueous acid and the cycloserine recovered by freeze drying or the addition of a water-miscible non-solvent, e.g. acetone. Cycloserine is a broad spectrum antibiotic useful in animal and poultry feed supplements; it is soluble in water, slightly soluble in glycols, isopropyl alcohol, methanol, ethanol, dioxane, 1-butanol and acetone; insoluble in hexane, benzene, chloroform, ether and petroleum ether; it contains 6 per cent hydrogen, 35.49 per cent carbon, 26.55 per cent nitrogen and 31.96 per cent oxygen; molecular weight 102; characteristic ultra-violet absorption at a wavelength of 224 microns; <FORM:0768007/IV(b)/1> , C=5.0 per cent, L=2.0 dm. 2N sodium hydroxide solution; gives a green colour with cupric ion in aqueous solution; gives a reddish brown with iron in aqueous solution; meltingpoint 155-157 DEG C.; exhibit characteristic absorption in infra red at 6.15, 6.55, 6.65, 7.20, 7.40, 7.50, 7.85, 8.20, 8.60, 8.80, 9.00, 9.40, 10.65, 10.90, 11.30, 11.40, 12.05, 12.50 and 13.25 microns: forms silver salt.