Patent GB-1303843-A (GB)
IPC: C07H17/08
Filed: 1970-02-03
Abstract: 1303843 Novel macrolide antibiotics MEIJI SEIKA KAISHA Ltd 3 Feb 1970 [25 Sept 1969] 36152/72 Divided out of 1303842 Heading C2A The novel macrolide antibiotics SFÀ837ÀA 2 , SF-837-A 3  and SF-837-A4, characterized by being white crystalline basic substances soluble in methanol, ethanol, acetone, chloroform, ethyl acetate, butyl acetate, acidified water, benzene, ethyl ether and carbon tetrachloride, and sparingly soluble or insoluble in petroleum ether, n-hexane and neutral water, being positive to the erythromycin test with 50% H 2 SO 4  but negative to ninhydrin and ferric chloride reagents, and containing only carbon, hydrogen, nitrogen and oxygen, the individual antibiotics being further characterized by the following properties:- are prepared by aerobically cultivating Streptomyces mycatofaciens (A.T.C.C. 21454) in an aqueous medium containing assimilable sources of carbon and nitrogen, recovering the said antibiotics from the culture and, if desired, separating them from one another. The antibiotics are recovered by extracting the optionally filtered culture with a water-immiscible solvent for the antibiotics at an alkaline pH; if the mycelium is filtered off, it may be extracted with aqueous acid which is then rendered alkaline and extracted with a water-immiscible solvent. The solvent extract may be concentrated to dryness to give a crude mixture of the antibiotics or this mixture or the solvent extract may be further processed to purify the mixture or separate it into the component antibiotics. Such processing includes repeated transfer between acid-aqueous solution and organic solvent solution, chromatography on, and serial elution from activated carbon, alumina, silica gel, or ion exchangers such as ion exchange-cellulose or -resin, and countercurrent distribution, e.g. between phosphate buffer and benzene. The antibiotics may be recovered from their purified solutions by concentration to dryness in vacuo, freeze drying, rendering an acidic aqueous solution alkaline to precipitate the free base or neutral to precipitate the acid-addition salt, or by addition of a miscible non-solvent. The antibiotics may be converted to their acid-addition salts (eg: tartrate or citrate) by treatment with the appropriate acid in aqueous or organic media, or to their acetyl derivatives by treatment with acetic anhydride in dry pyridine. The di-acetyl derivative of antibiotic SF-837-A 2  and the mono-acetyl derivative of antibiotic SF-837-A 3  and of antibiotic SF-837-A 4  are novel substances. Antibiotic SF-837-A 2  and its di-acetyl derivative probably have a structural formula wherein R 1 , R 2 , R 3  and R 4  mean -COCH 2 CH 3 , H, H and -COCH 2 CH 2 CH 3 , respectively, in the case of the said antibiotic; and -COCH 2 CH 3 ,  -COCH 3 , -COCH 3  and -COCH 2 CH 2 CH 3  respectively in the case of its diacetyl derivative. Antibiotics SF-837-A 3  and SF-837-A 4  and their mono-acetyl derivatives are believed to be of the general formula wherein R 1 , R 2  and R 3  have the following meanings: Pharmaceutical compositions having antibacterial activity against Gram-positive microorganisms comprise one or more of the aforesaid antibiotics, their non-toxic acid-addition salts and/or acetyl derivatives together with a pharmaceutically acceptable diluent or carrier: