During our continuing screening for new bioactive metabolites from fungi we discovered recently hexacyclinol(1) as a novel, unusual, oligocyclic metabolite in cultures of the fungal strain Panus rudis HKI 0254. The strain was isolated from basidiospores of this fungus found on dead betula woods collected near Irkutsk (Sibiria, specimen herb. H, DORFELT, Sibiria 299). Panus rudis is of widespread occurrence throughout the world in many different ecotypes and has been reported to produce bioactive secondary metabolites1,2). The basidiomata of Panus rudis from the Sibirian source are growing singly or basal confluent to little tufts, excentric to central, stipitate, infundibuliform, with hazel-brown, strong tomentous pilei until 4.5cm in diameter; pilei and stipes with hairs until 2.5mm, shows in cultures a white to light-brownish mycelium, tomentous with clamped connections.For cultivations a small piece of a mature slant culture of the strain HKI 0254 grown on malt extract agar (malt extract 4%, yeast extract 0.4%, agar 1.5%, deionized water ad 1 liter, pH 6.0) was used to inoculate 1000ml Erlenmeyer bottles containing 250ml of the producing medium consisting of glucose 1%, sucrose 1%, corn starch 1%, yeast extract 0.8%, casein peptone 0.1%, soybean meal 0.5%, (NH4)2HPO4 0.05%, CaCO3 0.03%, (NH4)SO4 0.5%.The fermentation broth (15 liters) was extracted twice overnight by stirring with ethyl acetate (1:1). The combined extracts were dried and evaporated to dryness Table 1.Structure elucidation of 1 (Fig. 1a) was done using optical spectroscopy, mass spectrometry, 1D and 2D NMR spectroscopy spectroscopy (1H, 13C Table 2) displayed signals of four methyl (1.78ppm, 1.78ppm, 1.28ppm, 1.15ppm), one methoxyl (3.01ppm), twelve methine and
From Penicillium janczewskii, obtained from a marine sample, two new diastereomeric quinolinones, 3S,4R-dihydroxy-4-(4'-methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (1) and 3R,4R-dihydroxy-4-(4'-methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (2), were identified, along with two known alkaloids, peniprequinolone (3) and 3-methoxy-4-hydroxy-4-(4'-methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (4). Cytotoxicity testing on eight tumor cell lines revealed a moderate specificity of 2 on SKOV-3 cells.
The three-dimensional solution structure of a DNA molecule of the sequence 5'-d(GCATCGAAAAAGCTACG)-3' paired with 5'-d(CGTAGCCGATGC)-3' containing a five-adenine bulge loop (dA(5)-bulge) between two double helical stems was determined by 2D (1)H and (31)P NMR, infrared, and Raman spectroscopy. The DNA in both stems adopt a classical B-form double helical structure with Watson-Crick base pairing and C2'-endo sugar conformation. In addition, the two dG/dC base pairs framing the dA(5)-bulge loop are formed and are stable at least up to 30 degrees C. The five adenine bases of the bulge loop are localized at intrahelical positions within the double helical stems. Stacking on the double helical stem is continued for the first four 5'-adenines in the bulge loop. The total rise (the height) of these four stacked adenines roughly equals the diameter of the double helical stem. The stacking interactions are broken between the last of these four 5'-adenines and the fifth loop adenine at the 3'-end. This 3'-adenine partially stacks on the other stem. The angle between the base planes of the two nonstacking adenines (A10 and A11) in the bulge loop reflects the kinking angle of the global DNA structure. The neighboring cytosines opposite the dA(5)-bulge (being parts of the bulge flanking base pairs) do not stack on one another. This disruption of stacking is characterized by a partial shearing of these bases, such that certain sequential NOEs for this base step are preserved. In the base step opposite the loop, an extraordinary hydrogen bond is observed between the phosphate backbone of the 5'-dC and the amino proton of the 3'-dC in about two-thirds of the conformers. This hydrogen bond probably contributes to stabilizing the global DNA structure. The dA(5)-bulge induces a local kink into the DNA molecule of about 73 degrees (+/-11 degrees ). This kinking angle and the mutual orientation of the two double helical stems agree well with results from fluorescence resonance energy transfer measurements of single- and double-bulge DNA molecules.
Cervimycins A-D are novel polyketide glycosides with significant activity against multi-drug-resistant staphylococci and vancomycin-resistant enterococci. They are produced by a strain of Streptomyces tendae, isolated from an ancient cave. The structures of the cervimycins were determined by performing extensive NMR and chemical degradation studies. All cervimycins have a common tetracyclic polyketide core that is substituted with unusual di- and tetrasaccharide chains, composed exclusively of trideoxysugars; however, they differ in the acetyl and carbamoyl ring substituent and in the highly unusual terminal methylmalonyl and dimethylmalonyl residues.
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