Patent GB-1254136-A (GB)
Title: New antibiotic sf-767-a and sf-767-l substances, and process for the production of theses substances
IPC: G11B33/02
Filed: 1969-05-22
Abstract: 1,254,136. Antibiotics SF-767-A and SF-767-L. MEIJI SEIKA KAISHA Ltd. 22 May, 1969 [24 May, 1968; 28 June, 1968], No. 26051/69. Heading C2A. The novel antibiotics SF-767-A and SF- 767-L or their acid addition salts are obtained by aerobically cultivating Streptomyces microsporeus A.T.C.C. 21384, or a strain thereof producing the said substances, in a medium containing assimilable sources of carbon and nitrogen. Each substance inhibits the growth of Gram-negative; Gram-positive and acid-fast bacteria; is soluble in water, slightly soluble in methanol, and nearly insoluble in ethanol, butanol, acetone, ethyl acetate, benzene, ethylether and n-hexane; has no U.V. absorption between 210 and 360 mÁ; is positive to the Molisch, anthrone and ninhydrin tests but negative to the Benedict, Fehling, Sakaguchi, FeCl 3 , Elson-Morgan and maltol tests; gives a weakly alkaline dextro-rotatory solution in water; migrates towards the cathode on electrophoresis at pH 1À8; and is an aminoglycosidic substance containing C, N, O and H, with the amino group present but no acidic groups. SF-767-A is a white amorphous powder decomposing with gas-evolution at about 190‹ C.; having the elementary composition 45À06% C, 7À40% H, 8À90% N, 39À08% O; a molecular weight of 620; empirical formula C 23 H 44 N 4 O 15 ; an optical rotation of [α]D = + 67 degrees in 1% aqueous solution; and an I.R. absorption spectrum as shown in Fig. 2 above with bands at the wave numbers: 3400, 2900, 1595, 1460, 1350, 1130 (shoulder) and 1010 cm.<SP>-1</SP>. SF-767-L is a white amorphous powder decomposing with gas evolution at about 192‹ C.; having the elementary composition 43À58% C., 6À80% H, 8À62% N, 40À75% O; a molecular weight of 682; empirical formula C 23 H 46 N 4 O 16 ; an optical rotation of [α]D = + 69 degrees in 1% aqueous solution; and an I.R. absorption spectrum as shown above in Fig. 5 with bands at the wave numbers: 3420, 2910, 1585, 1480, 1350, 1130 (shoulder) and 1010. SF-767-A is produced throughout the fermentation whereas SF-767-L tends to be formed in the latter stages thereof; also incubation below 30‹ C. favours formation of the first-mentioned substance, and production of the latter substance is encouraged above 30‹ C. The antibiotics may be recovered from the culture medium by absorption on charcoal at alkaline pH followed by elution at acid pH; or by absorption on and elution from ion exchange resin; or by precipitation with a water-miscible organic solvent, if required in the presence of an acid, when the precipitate is the acid-addition salt. They may be purified by ion exchange chromatography, and the solutions concentrated to dryness to give the solid antibiotic. The two antibiotics may be separated by absorption from aqueous solution on to a cationexchange resin column followed by elution with dilute ammonia, when the SF-767-L elutes first. The separate antibiotics are converted to their N-acetylates with acetic anhydride in methanol; also their sulphate addition salts are prepared. Pharmaceutical compositions comprise the antibiotics SF-767-A or SF-767-L or their sulphate salts in aqueous injectable solution.