A new antibiotic SF-2370 produced by Actinomadura.

Sir: A new indolocarbazole antibiotic SF-2370 has been found in the culture broth of Actinomadura sp. SF-2370 which was isolated from a soil sample collected at Shimizu, Shizuoka Prefecture, Japan. The antibiotic is weakly active against some bacteria and fungi. In this communication, the isolation, characterization, and structural elucidation by the spectral studies are reported. Actinomadura sp. SF-2370 was cultured at 28°C for 5 days in a medium (600 ml) containing glucose 1.5%, wheat germ 1.0%, corn steep liquor 1.0%, Pharmamedia (Traders Protein, Buckeye Cellulose Corp.) 0.5 %, CaCO3 (adjusted to pH 7.0) 0.3% in a 1-liter jar fermentor. Vegetative inoculum, 20 ml (3.3%) grown on a rotary shaker for 7 days at 28°C in a medium containing glucose 2.0%, wheat germ 1.0%, peptone 0.5%, yeast extract 0.5% and CaCO, (adjusted to pH 7.0) 0.1 % was used. The antibiotic was assayed by the paper disc method against Micrococcus luteus. The culture broth was filtered at pH 7.8 and the antibiotic in the mycelium was extracted with 70% aqueous acetone (500 ml). The extract was concentrated to remove acetone and the antibiotic in the concentrate was extracted twice with EtOAc (250 ml). The extract was dried on Na2SO4 and concentrated to give an oily residue. n-Hexane was added to the residue to give the precipitates (286 mg). The precipitates were chromatographed on a column of silica gel (60 ml) developed with chloroform EtOAc (10: 1) to yield a pale yellow powder (216 mg). The powder was further purified by preparative TLC using EtOAc (Rf 0.31) as a developing solvent. Recrystallization from MeOH gave pale yellow crystals of antibiotic SF-2370 (79 mg) (1): mp 261-262-C (dec), [a] 1 +57° (c 0.1, MeOH). Anal Calcd for C27H21N3O,: C 69.38, H 4.50, N 8.99. Found: C 69.50, H 4.74, N 8.88. MS m/z obsd: 467.1473 (M+), calcd for C27H21N3O5: 467.1479. UV ),,',11.0.11 nm (E; m) 228 (725), 250 (717), 265 (sh), 280 (sh), 290 (1,708), 320 (sh), 335 (432), 350 (325) and 367 (353). No characteristic shifts on UV absorption maxima were observed in acidic and alkaline solutions. IR v,,,as (KBr) cm-1 3400 (OH, NH), 1730 (ester), 1670 (amide), 1455, 1255 (ether) and 750 (aromatic). 'H and 13C