Patent GB-841495-A (GB)
Title: A new antibiotic designated compound number 58
Filed: 1958-01-16
Abstract: <PICT:0841495/IV(b)/1> A new antibiotic designated Compound No. 58 is obtained by p  cultivating a Compound No. 58-producing strain of Streptomyces fasciculus e.g. S. fasciculus ATCC 12703 (described) in a nutrient medium containing a source of carbon and nitrogen under submerged aerobic conditions.  A temperature of 24 DEG  to 35 DEG  C. and a duration of cultivation of 1 to 6 days is suitable.  Specified carbon sources are sugars, starch, glycerol and corn meal.  Nitrogen sources are casein, soybean meal, peanut meal, wheat gluten, cottonseed meal, lactalbumin, tryptone and enzymatic digest of casein.  Other additions are (a) growth substances such as distiller's solubles, yeast extract and molasses fermentation residues; (b) mineral salts such as sodium chloride, calcium carbonate, potassium phosphate, sodium nitrate and magnesium sulphate; and (c) trace metals.  Compound No. 58 is isolated from the broth by filtration using a filter aid and extraction of the mycelium cake with an alkanol such as methanol, ethanol, butanol and pentanol. The extract is concentrated in vacuo and the residue treated with a non-solvent such as hexane and the solid Compound No. 58 filtered off.  Compound No. 58 has fungicidal activity and in the crude or purified form is formulated into compositions for the treatment of plants (see Group VI).  It is an amphoteric compound forming salts with acids such as sulphuric, hydrochloric, nitric, hydrobromic, benzene sulphonic, toluene sulphonic, trichloracetic and sulphurous, and with bases such as hydroxides and oxides of the alkali metals and alkaline earth metals and triethylamine sulphate; gives violet colour with conc.H2SO4; in 70% n-propanol water has R6 value of 0.70; is soluble in pyridine and N,N-di-methylformamide, insoluble in water, methyl isobutyl ketone, benzene, nitromethane, acetonitrile, ethyl acetate and methylcyclohexane; decomposes at 123 DEG  C., melts at 250 DEG  C.; [a ]5D = + 302 DEG  (0.2% pyridine); contains carbon 59.94%, hydrogen 8.29%, nitrogen 1.96% and oxygen 29.81%; ultraviolet absorption in 80% aqueous methanol 0.001 N in NaOH e 1%1 cm = 1238 at 349 mm , = 1200 at 332 mm , = 753 at 317 mm  and = 358 at 303 mm ; infrared absorption spectrum exhibits peaks at 3279, 2865, 1712, 1695, 1613, 1560, 1414, 1368, 1168, about 1099, 1066, 1006, 963, 918, 885, 842 and 789 reciprocal centimetres (Fig. II).  In examples: (a) the sodium salt is prepared by adding methanolic sodium hydroxide to a solution of compound number 58 in methanol (b) compound number 58 is obtained from the sodium salt by adjusting a methanol solution of the sodium salt to pH 7.0 by means of phosphoric acid; (c) the triethylamine sulphate salt is prepared by adding triethylamine sulphate to a methanol solution of compound number 58 and adding acetone to precipitate the said salt; (d) the sulphate and hydrochloride are prepared by adding sulphuric acid or hydrochloric acid to an acetone solution of compound number 58 to pH 3.2 and precipitating by means of ethyl acetate.ALSO:A fungicidal composition comprises an inert carrier and at least three parts per million of the antibiotic, compound number 58, or a salt thereof such as the sulphate, hydrochloride, hydrobromide, hydroiodide, benzene sulphonate, toluene sulphonate, trichloracetate and the sodium, potassium, barium, lithium and calcium salts.  Compound number 58 may be used in the form of the whole broth, as such or concentrated, the mycelium cake or as the purified product.  Sprays, emulsions, injectionable solutions, suspensions and dusts are used containing 0,01 to 95% of the antibiotic.  Suitable carriers are pyrophilite, bentonite, talc, kaolin, clay, waxes and resins including natural resins or gums. Stabilisers and spreading agents may also be present. A spray may be prepared by suspending the antibiotic in 5% aqueous acetone.