PROCESS FOR PRODUCING POLYENE-TYPE 67-121 ANTIBIOTIC-COMPLEX AND COMPONENTS THEREOF

摘要

1474879 Antibiotic complex SCHERICO Ltd 6 March 1975 [11 March 1974] 9392/75 Heading C2A The invention is directed to a polyene antibiotic complex designated 67-121 complex, in free form or in the form of a pharmaceutically acceptable derivative. The complex in the free form has the following characteristics; ultraviolet absorption maxima in methanol at 342, 363, 382 and 403 mÁ with corresponding E1% 1cm values of 340, 475, 667 and 605, infra-red absorption maxima in mineral oil at 3350, 1725 and 1665 cm-1 and nuclear magnetic resonance spectra in hexa-deutero-dimethylsulfoxide with maxima at 2À75, 6À56 and 7À64 p.p.m. The complex comprises antibiotic components 67- 121A, 67-121B, 67-121C and 67-121D. The complex or a component antibiotic thereof may be prepared by cultivating a microorganism of the species Actinoplanes coerulus in a nutrient medium under aerobic conditions until substantial antibiotic activity is generated. The preferred microoganism is the strain Actinoplanes coeruleus NRRL 5325. Antibiotic 67-121A, in the free form has the following characteristics, ultra-violet absorption maxima in a 4 : 1 tetrahydrofuran : water mixture of 408, 384 and 363 mÁ with corresponding E1% 1cm values of 950, 1100 and 680; infra-red absorption maxima in mineral oil at 3350, 1725 and 1665 cm-1 and a nuclear magnetic resonance spectrum in hexa-deutero-dimethylsulphoxide with maxima at 2À73, 6À55 and 7À64 p.p.m. Antibiotic 67-121B, in the free form has the following characteristics ultra-violet absorption maxima in a 4 : 1 tetra hydrofuran : water mixture of 408, 383 and 362 mÁ with corresponding E1% 1cm values of 620, 750 and 490; infra-red absorption maxima in mineral oil at 3350, 1725 and 1665 cm-1 and a nuclear magnetic resonance spectrum in hexa-deutro dimethylsulphoxide with maxima at 6À58 and 7À60 p.p.m. Antibiotic 67-121C, in the free form has the following characteristics, ultraviolet absorption maxima in 4 : 1 tetrahydrofuran : water mixture of 408, 383 and 362 mÁ with corresponding E1% 1cm value of 800, 910 and 600; infra-red absorption maxima in mineral oil at 3350, 1725 and 1665 cm-1 and a nuclear magnetic resonance spectrum in hexa-deutero dimethylsulphoxide with maxima at 2À76, 6À57 and 7À65 p.p.m. The polyene antibiotics are further characterized as a heptaene subgroup II antibiotic and having an aromatic moiety of the formula in which for antibiotics 67-121A and C, R is methyl and/or antibiotic 67-121B, R is H. The antibiotics 67-121A and 67-121B are further characterized by a presence of a D- mycosamine sugar unit glycosidically attached to an allylic hydroxy group of the aglycone structure and antibiotic 67-121C is further characterized by the presence of the disaccharide unit [O-#-D-mannopyranosyl(1#4)-D- mycosamine]glycosidically attached to an allylic hydroxy group of the aglycore structure. The complex or components may be in a free form or in the form of a pharmaceutically acceptable derivative. The antibiotic substances may be admixed with a suitable pharmaceutically acceptable carrier. The antibiotic substance may be administered to animals having a fungal infection to elicit an anti-fungal response therefrom.