Abstract
During the course of searching for bioactive compounds from microbial origin, we isolated Streptomyces sp. GK9244 from soil sample collected in Taejon, Korea, which produced two-type polyenes, cytotoxic and antifungal tetrin C (1) and cytotoxic and antibacterial 16-methyloxazolomycin (2) together with several related compounds. The stereostructures of 1 and 2 have been elucidated on the basis of NMR data and chemical transformations. The filtrates from culture broth of Streptomyces sp. GK9244 were passed through a Diaion HP-20 with H_2O followed by MeOH and solvent partition of the MeOH eluate was carried out. Cytotoxic n-BuOH and CH_2Cl_2 layer were subjected to a series of ODS flash chromatography, Sephadex LH-20 gel-filtration, and ODS HPLC with aquous MeOH to yield 1 and 2. Molecular formulas of 1 and 2 were established as C_<34>H_<49>NO_<13> and C_<36>H_<51>N_3O_9 from HRFABMS and ^<13>C NMR data, respectively. The gross structure of 2 was identical to that of main metabolite, tetrin B, except for the epoxy group at C-4 and C-5. To determine the absolute stereochemistry of tetrin C, its chemical degradation fragments were examined by the modified Mosher's method. The planar structure of 1 was mainly determined by interpretation of 2D NMR spectra to be a triene including a spiro β-lactone-γ-lactam system and an oxazole ring. Its stereochemistry was determined by the NOESY data and chemical transformations. Tetrin C (1) and 16-methyloxazolomycin (2) were cytotoxic (4.6μg/mL and 0.23μg/mL against P388 murine leukemia cells, respectively). Tetrin C also showed antifungal activity against Mortierella ramannianus (MIC, 5.0μg/mL) and Phenicillium chrysogenum (10μg/mL), while 16-Methyloxazolomycin exhibited antibacterial activity against Bacillus subtilis 1069 (5.0μg/mL) and Chlorella vulgaris IFO 15941 (10μg/mL).
