ISOLATION, STRUCTURE DETERMINATION AND BIOLOGICAL ACTIVITIES OF A NOVEL ANTIFUNGAL ANTIBIOTIC, S-632-C, CLOSELY RELATED TO GLUTARIMIDE ANTIBIOTICS

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A new antifungal antibiotic, S-632-C, was extracted with ethyl acetate from the culture filtrate of Streptomyces hygroscopicus S-632 and isolated through a combination of column and preparative thin-layer chromatographies on silica gel. The structure of S-632-C was determined by analysis of ¹H and ¹³C-NMR, MS, UV and IR spectra in comparison with those of S-632-A₂ (9-methylstreptimidone). The signals were assigned on the basis of 2D NMR experiments, which involved ¹H-¹H DQF COSY, HMQC and HMBC spectral analysis. From these results, the chemical structure of S-632-C was elucidated as 6-(3, 5-dimethyl-2-oxo-4, 6-octadienyl)-4-carbamoylmethyl3, 4, 5, 6-tetrahydro-2-pyrone. The antibiotic exhibited exclusively weak in vitro antifungal activity against Saccharomyces spp. and similar cytotoxic activity against KB carcinoma cells, as compared with the glutarimide antibiotic S-632-A₂. In addition, this antibiotic had the ability to change the morphology of ras^ts-transformed NRK cells to that of normal cells, also a characteristic S-632-A₂ and B₁.