Isolation of New Anthracycline

Sir: During the course of our screening program for new anthracycline antibiotics, four /5-rhodomycinone glycosides, A447 A, B, C and D were found in the acetone extract of cultured mycelia of a strain designated as A447. Based on NMR spectral analysis and chemical degradation, A447 A and B were identified as cosmomycins D and C1^, respectively, while A447 C and D were found to be new congeners. A447 C and D inhibited the growth of P388 murine leukemia cells at the IC50 values of2.9 ng/ml and 1.4 ng/ml, respectively. Strain A447was isolated from a soil sample collected at Hachijyo-island, Tokyo, Japan, and the taxonomic studies identified that the strain belongs to Streptomyces cyaneus. A detailed description of the classification will be reported in due course. The organism was cultivated at 27°C for 48 hours in a 50-liter jar fermentor containing 30 liters of a mediumconsisting of glucose 2.5%, soybean meal 1.5%, dry yeast 0.2% and calcium carbonate 0.4 % (pH 7.0). The mycelial cake obtained by filtration was extracted with acetone and the extract was concentrated. The aqueous residue, after being adjusted to pH 8.5, was extracted with ethyl acetate. The organic solvent layer was evaporated in vacuo and the dried material was dissolved in a small volume of acetic acid and diluted with 10 volumes of water. This solution was washed with chloroform and then adjusted to pH 8.5 with 5 n NaOH followed by extraction with chloroform. The chloroform solution was dried over anhydrous sodium sulfate and concentrated to dryness to give an anthracycline mixture containing A447 A, B, C and D. This material was chromatographed on preparative silica gel TLC plates with CHC13 MeOH 28% NH4OH (200:20: 1). Each separated band corresponding to A447 A, B, C and D was scraped off and eluted with CHCl3MeOH (10: 1) followed by evaporation to dryness in vacuo. These four fractions were further puriJAN. 1987