| 摘要 |
1,226,494. Antibiotic 20,798 R.P. RHONEPOULENC S.A. 4 March, 1969 [5 March, 1968], No. 11486/69. Heading C2A. The novel antibiotic 20,798 R.P. of formula is produced by aerobically cultivating Streptomyces coerulearubidus NRRL 3045 (also known as Streptomyces 31723), or a 20,798 R.P.-producing mutant thereof, in a nutrient medium containing assimilable sources of carbon, nitrogen and inorganic substances, and separating the required antibiotic from the culture medium. The antibiotic is basic, and consists of orangered needle-like crystals, melting at 225‹ to 230‹ C., soluble in water and alcohols, sparingly soluble in CHCl 3 and nearly insoluble in benzene and diethyl ether, having an optical rotation: [α]20 = Œ 191 degrees + 10 degrees D (c = 0.2, ethanol containing 0.1% of N.HCl), and an adsorption spectrum in the U.V. and visible ranges with peaks at 234, 252, 290 and 475 mÁ, troughs at 242, 280 and 320 mÁ, and shoulders at 219, 228, 272, 533 and 553 mÁ, and in the I.R. as shown in Fig. 1. 20,798 R.P. is isolated from the medium, which also contains the antibiotic 9865 R.P. comprising a mixture of antibiotics 13,057 R.P. (Daunomycin), 13,213 R.P. and 13,330 R.P., by extracting the medium at pH 5.5 to 9.0 with a butanol (except t-butanol), ethyl acetate or chloroform, optionally after filtering off the mycelium either at pH 1.5 to 2.0 in the presence of oxalic acid or at pH 2.0 to 7.0 in the presence of a C 1 to C 3 alkanol. The extraction may be preceded by treatment of the medium at pH 4.0 with cationic exchange resin followed by elution of the required material with acid or saline aqueous methanol. The solvent extract is then concentrated, brought to pH 4.0, and a non-solvent for the antibiotic, e.g. hexane, is added. The precipitated crude mixture is separated into its components by e.g. chromatography, countercurrent distribution, or partition between different solvents. R.P. 20,798 is finally crystallized as the hydrochloride salt. The antibiotic may be hydrolysed in acid medium to yield the aglycone of formula melting at 285‹ C., and an amino-sugar. Pharmaceutical compositions having antibiotic and antitumoral properties, comprise 20,798 R.P. or a salt thereof, together with a pharmaceutically acceptable carrier or diluent and/or another antibiotic. They may be in forms for oral or parenteral administration. Reference has been directed by the Comptroller to Specification 1,188,262. |
