In a study to discover potential anticancer agents from rhizosphere fungi of Sonoran desert plants cytotoxic EtOAc extracts of four Aspergillus strains have been investigated. Two new metabolites, terrequinone A (1) and terrefuranone (2), along with Na-acetyl aszonalemin (LL-S490beta) (3) were isolated from As. terreus occurring in the rhizosphere of Ambrosia ambrosoides, whereas As. terreus inhabiting the rhizosphere of an unidentified Brickellia sp. afforded dehydrocurvularin (4), 11-methoxycurvularin (5), and 11-hydroxycurvularin (6). As. cervinus isolated from the rhizosphere of Anicasanthus thurberi contained two new compounds, 4R*,5S*-dihydroxy-3-methoxy-5-methylcyclohex-2-enone (7) and 6-methoxy-5(6)-dihydropenicillic acid (8), in addition to penicillic acid (9). Penicillic acid was also isolated from As. wentii occurring in the rhizosphere of Larrea tridentata. The structures of 1-9 were elucidated by spectroscopic methods and chemical derivatizations. Acetylation of 2 afforded 14-acetylterrefuranone (13) and 14-deoxy-13(14)-dehydroterrefuranone (14). Metabolites 1-9, the dienone 14, and 5(6)-dihydropenicillic acid (16) were evaluated for cytotoxicity in a panel of four human cancer cell lines and in normal human primary fibroblast cells. Compounds 4 and 5 displayed considerable cytotoxicity, whereas 1, 6, 9, and 14 were found to be moderately active, with 6 and 9 exhibiting selective cytotoxicity against cancer cell lines compared with the normal fibroblast cells.

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.

Polyketides form a major class of secondary metabolites of bacteria, fungi, and plants with broad structural diversity as a result of dense functionalization and spatial properties. [1] Many polyphenolic derivatives have found considerable interest as pharmaceuticals, biological tools, and dyes. A hallmark of aromatic polyketides is their common biogenesis from simple acyl and malonyl units through the action of different types of iterative polyketide synthases. [2][3][4][5] The orchestrated assembly and processing of the biosynthetic intermediates gives rise to polyphenolic compounds that differ widely in the number of carbocycles they contain, their topology, and the substitution of the rings. [4,6] From a structural point of view, it is remarkable that only a limited number of carbocyclic (aromatic) polyketide frameworks occur naturally. Linear and monoangular polyphenolic ring systems are found almost exclusively (Scheme 1); perifused carbocycles, in which rings are fused through more than one face, are rarities. A possible rationale for this observation is the preferred U-shaped folding of a nascent poly-b-keto chain. S-shaped cyclization patterns, as in the biosynthesis of the pentacyclic "discoid" Streptomyces naphthanthrene metabolites resistomycin and resistoflavin, are clear exceptions. [7][8][9][10][11] Some phenalenes and benz [d,e]anthracenes from plants and fungi are probably also formed by an alternating polyketide folding pattern, [12,13] whereas the biosynthesis of phenylphenalenones involves intramolecular cycloaddition with a cinnamoyl-derived moiety.[14] Homologous tetracyclic pyrenes thought to be derived from phenanthrenes have been isolated from Uvaria and Juncus spp. [15,16] An important example of a perylene is altertoxin, [17] which is formed by naphthol dimerization in analogy with the hypericin [18] biosynthetic pathway. To date, however, a significant gap has remained between the pentacyclic pentangular [19,20] and discoid [8] polyketide structures: the benzo[a]pyrene scaffold. Benzo[a]pyrenes are only known as notorious products of the pyrolysis of organic matter which are transformed into carcinogens upon epoxidation. [21][22][23] No example of the biogenesis of a related carbocyclic system has been described. Herein, we report the first discovery of a natural product with a benzo[a]pyrene framework.During the course of metabolic profiling of the ketalin producer Streptomyces lavendulae (strain Tü 1668), [24] we noted the formation of minute amounts of a novel aromatic compound with UVabsorptions at l max = 417, 251, and 217 nm when the strain was cultured on a large scale (2 50 L). Highresolution EIMS provided sufficient evidence that the compound had not been described previously. The crude extract was subjected to purification first with amberlite XAD16, then by reversed-phase flash chromatography (RP18) and subsequent open-column chromatography on Sephadex LH-20 and silica gel. The new compound 1 (7 mg in total) was isolated as a yellow solid. A series of biological assays with ...

Four new griseusins, 4'-dehydro-deacetylgriseusin A (1) and 2a,8a-epoxy-epi-deacetylgriseusin B (2) as new constitutional derivatives and epi-deacetylgriseusin A (3) and epi-deacetylgriseusin B (4) as new stereoisomers, were isolated from Nocardiopsis sp. (YIM80133, DSM16644). 4'-Dehydro-deacetylgriseusin A (1) showed pronounced cytotoxic potency (mean IC50 = 0.430 microM) combined with a significant selectivity for mammary cancer, renal cancer, and melanoma in a panel consisting of 37 tumor cell lines. In a clonogenic assay with tumor cells from 51 solid tumors, 1 inhibited anchorage independent growth and in vitro colony formation of tumor cells in a concentration-dependent and tumor type selective manner. As 1 was only a minor product, a semisynthetic preparation from the major metabolite, epi-deacetylgriseusin A (3), was achieved. Our studies also yielded 9-hydroxy-epi-deacetylgriseusin B methylester (5), 4'-dehydro-9-hydroxy-deacetylgriseusin B methylester (6), and 4'-dehydro-2a,8a-epoxy-deacetylgriseusin B (7) as new synthetic isochromanequinone derivatives, which provided a basic structure-activity relationship study.