Chemical examination of two marine Streptomycetes has resulted in the isolation of four new butenolides, namely 4,10-dihydroxy-10-methyl-dodec-2-en-1,4-olide (1), two diastereomeric 4,11-dihydroxy-10-methyldodec-2-en-1,4-olides (2/3), and 4-hydroxy-10-methyl-11-oxo-dodec-2-en-1,4-olide (4). The structures were identified by interpretation of the 2D NMR and mass spectral data.Butenolides, a family of R, -unsaturated lactones, are often encountered among fungi, 2 bacteria, 3 and gorgonians, 4 to name a few. Their saturated analogues act as signaling substances in bacteria 5 and enhance spore formation of Streptomycetes or induce metabolite production. 6 In a continuing search for bioactive constituents from marine microorganisms, we found that extracts from the Streptomycete strains B 5632 and B 3497 from marine sediments formed several new butenolides.The isolate B 5632 was fermented in a 20-L scale on YMG medium with artificial seawater for 3 days. The fermentation broth was filtered over Celite and exhaustively extracted with ethyl acetate. This extract was partitioned between methanol and cyclohexane for defatting, and the methanol layer, after concentration, was chromatographed on a flash column. Bioassay-guided fractionation led to the localization of the activity from which four known antimycins and three new butenolides (1-3) were obtained. In a similar way, strain B 3497 delivered a new keto butenolide (4) in addition to antimycin A. The antimycins were responsible for the strong antifungal activity of the extracts against Mucor miehei (Tü 284).Analytical HPLC indicated that the butenolide fraction (localized by a strong blue-violet color on spraying with anisaldehyde) contained two related compounds. Compound 1 was obtained as an oil by preparative HPLC. Under EIMS conditions, no molecular ion was visible; however, its molecular mass was fixed as 226 Da by pseudomolecular ions at m/z 244 [M + + NH 4 ] and 226 [M + + NH 4 -H 2 O] on CIMS. An APT spectrum showed that the compound contained two methyl, six methylene, three methine, and two quaternary carbons, according to a formula C 13 H 22 O 3 , in agreement with chemical shifts. The proton signals at δ 7.44 and 6.11 and a carbon signal at δ 173.2 indicated that the compound had an R, -unsaturated lactone, ester, or acid moiety. The molecular formula demands three double-bond equivalents. As two are accounted for by an ester or lactone carbonyl and a double bond, the molecule must be monocyclic. The H-H COSY spectrum showed couplings between the two olefinic protons and a multiplet at δ 5.01, indicating an oxygenated carbon next to the double bond. This methine showed further coupling to two methylene protons, which, in turn, were coupled to another methylene group. An HMQC spectrum correlated the proton signal at δ 5.01 to a methine signal at δ 83.4. This sequence resulted in fragment a.Additionally, the 1 H NMR spectrum showed a clear quartet and a triplet, indicating the presence of an isolated ethyl group in the molecule. A signal for an isolated me...

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Three new sesquiterpene quinols (1, 2, and 5) and two known ones (3 and 4) were isolated along with halistanol sulfate (6) from a marine sponge of the genus Aka collected from Yap Island, Federated States of Micronesia. Their structures were determined from spectral data, and the structure of siphonodictyal C (3) was revised. Sulfates 3 and 6 inhibit CDK4/cyclin D1 complexation, whereas 1 and 4 do not.

Two new cyclodepsipeptides designated bacillistatins 1 (1) and 2 (2) have been isolated from cultures of a sample of Bacillus silvestris that was obtained from a Pacific Ocean (southern Chile) crab. Each 12-unit cyclodepsipeptide strongly inhibited growth of a human cancer cell line panel, with GI 50 s of 10 −4 -10 −5 μg/mL, and each compound was active against antibiotic-resistant Streptococcus pneumoniae. The structures were elucidated by a combination of X-ray diffraction and mass and 2D NMR spectroscopic analyses, together with chemical degradation.Marine microorganisms are rapidly becoming a very useful source of new cancer cell growth inhibitory substances that have unique structures. Illustrative are recent examples of antineoplastic substances from marine bacteria, 1a-h fungi, 2a-h cyanobacteria, 3a-e and dinoflagellates. 4a-d As part of our extended evaluation of terrestrial and marine microorganisms as sources of new anticancer drug candidates, we collected a marine crab on Chiloé Island, Chile, in 1998. A Bacillus species, subsequently identified as B. silvestris, was isolated from the crab, and extraction of the scaled up bacterial broth has led to the identification of two new cyclodepsipeptides with antibacterial and human cancer cell line inhibitory activity. Bioactive cyclodepsipeptides have been isolated previously from other Bacillus species, including B. cereus ,5a, d B. polymyxa ,5c and B. natto. 5b Members of the genus Bacillus are common in both terrestrial and marine sediments. Bacillus silvestris was first described in 1999, when it was isolated from a sample of forest soil in Germany, 6a and more recently it was identified in water samples taken from the southern Baltic Sea, a brackish environment. 6b Results and DiscussionThe Bacillus silvestris culture was scaled up and extracted as described in the Experimental Section to give a dark-brown gum (3.14 g; P388 lymphocytic leukemia: ED 50 0.0066 μg/mL), which was shown by HPLC analysis to comprise a mixture with at least six closely spaced peaks. Subsequent high-resolution LC-MS showed the mixture to be more complex than was apparent from the HPLC analysis (Table 1).Attempts at separation by way of gel permeation and partition chromatography using Sephadex LH-20 and silica gel Lobar C 8 columns were unsuccessful. Separation using an Ito multi-layer † Dedicated to Dr. David G. I. Kingston of Virginia Polytechnic Institute and State University for his pioneering work on bioactive natural products. ‡ Dedicated also to Diane Middlebrook Djerassi (1939Djerassi ( -2007 Table 1 shows that 1 and 2 have molecular weights a little higher than that of the antibiotic valinomycin (3).By X-ray crystallographic analysis of 1 (Figure 1), its structure was shown to be a 36-membered cyclodepsipeptide that incorporates R-valine (R-Val), S-lactic acid, (S-Lac), S-valine (S-Val), and 2R-hydroxy-3S-methyl-valeric acid (2R-Hy-3S-Me-v) and that closely resembles 3, which consists of three repeating sequences of R-Val, S-Lac, S-Val, and 2R-hydroxyisova...

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From a terrestrial Streptomycete, GW 10/2517, the new 5-(2-methylphenyl)-4-pentenoic acid (1a) was isolated. The structure of 1a was proven by a detailed spectroscopic analysis and by synthesis.

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A Streptomyces sp. isolated from riverbank soil in Manitoba, Canada, was found to contain two cancer cell growth inhibitories: diazaanthraquinone 1 and 3-(hydroxyacetyl)indole (8). The structures were determined by interpretation of data from HRMS, UV, and high-field (400 MHz) NMR experiments. The red-colored diazaanthraquinone 1 and 3-(hydroxyacetyl)indole (8) were found to inhibit (0.1-3 microg/mL) growth of a minipanel of human cancer cell lines and P388 lymphocytic leukemia cells. Diazaanthraquinone 1 was also found to inhibit growth of the bacteria Streptococcus pneumoniae and Neisseria gonorrheae. However, three companion constituents, cyclo-Pro-Leu (5), cyclo-Pro-Phe (6), and cyclo-Pro-Val (7), did not inhibit cancer cell growth.