GB1281605A - Antibiotic am374 and production thereof - Google Patents

Abstract

1281605 Antibiotic AM 374 AMERICAN CYANAMID CO 13 April 1970 [14 April 1969] 17470/70 Heading C2A The novel antibiotic AM 374 having the following characteristics: Analysis: C = 54À54%, H=6À10%, O=29À01%, N=7À60%, and Cl=2À47%; Melting point indefinite, decomposing above 250‹ C.; Optical rotation, [α] D <SP>25</SP> = - 102Œ2À9 degrees (C= 1À045 in water); U.V. maxima, in acidic solution = 282 mÁ (E<SP>1%</SP> 1cm. =42); in neutral solution = 282 mÁ (E<SP>1%</SP> 1 cm = 42À5); in basic solution = 305 mÁ (E<SP>1%</SP> 1 cm. = 51À5) and 260mÁ (shoulder) (E<SP>1%</SP> 1 cm. = 92); I.R. absorption peaks at 3À0, 3À45, 6À0, 6À2, 6À3, 6À67, 6À88, 7À05, 7À22, 7À35 (shoulder), 7À52, 7À67, 8À2, 8À65 (shoulder), 8À85, 9À45, 9À75, 9À90, 1045, 1107, 11À5, 12À0, 12À35, 13À35 and 14À4 Á, as shown in the drawing and being readily soluble in water and dimethylsulphoxide, sparingly soluble in ethanol, and moderately soluble in methanol, is prepared by aerobically cultivating Streptomyces eburosporeus NRRL 3582 or an AM 374-producing strain thereof, in aqueous nutrient medium. The antibiotic is isolated from the filtered medium by adsorption on charcoal, eluting therefrom with 40% aqueous acetone brought to pH 2À0 with H 2 SO 4 , concentrating the eluant and removing the sulphuric acid by precipitation with barium hydroxide and adsorbing the antibiotic from the filtered solution on acidified alumina. It is eluted with 25-50% aqueous methanol, concentrated and lyophilized to give a crude product. This may be purified by adsorption on ion-exchange resin, elution with dilute sulphuric acid and removal of the latter with barium hydroxide, after which the pH is brought to 8À0 and the pure antibiotic is precipitated by addition of acetone, filtered off and dried. The antibiotic may be converted to its acidaddition salts, e.g. the sulphate or chloride. By treatment with boiling aqueous hydrochloric acid, AM 374 is converted to an antibiotically active hydrolysis product, characterized by: Analysis: C=62À54%, H=5À81%, O= 25À52%, N=8À32% and Cl=7À11%; Optical rotation, [α]<SP>25</SP> D = - 69Œ3À6 degrees (C=0À839 in water) and I.R. absorption peaks at 3À0, 3À3 (shoulder), 3À43, 5À75 (shoulder), 5À92 (shoulder), 6À0, 6À15 (shoulder), 6À25, 6À48 (shoulder), 6À68, 6À85, 7À03, 7À18, 7À5, 7À67, 7À95 (shoulder), 8À3, 8À55 (shoulder), 8À86, 9À15, 9À45, 9À9, 10À45 (shoulder), 11À1, 11À55 (shoulder) 11À9, 13À3 and 14À4 Á. Antibiotic AM 374, its salts and its hydrolysis product may be incorporated into animal feedstuffs or pre-mix concentrates therefor. Pharmaceutical compositions for oral or injectable administration comprise antibiotic AM 374, its non-toxic salts or its hydrolysis product together with a pharmaceutical excipient or carrier.