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Six new 6-isopentylsphaeropsidones, strobiloscyphones A–F (1–6), and a new hexadecanoic acid, (2Z,4E,6E)-8,9-dihydroxy-10-oxohexadeca-2,4,6-trienoic acid (7), together with sphaeropsidone (8) and its known synthetic analogue 5-dehydrosphaeropsidone (9) were isolated from Strobiloscyphasp. AZ0266, a fungus inhabiting the leaf litter of Douglas fir (Pseudotsuga menziesii). The structures of 1–7were established on the basis of their high-resolution mass and 1D and 2D NMR spectroscopic data, and their relative and/or absolute configurations were determined by NOE, comparison of experimental and calculated ECD spectra, and application of the modified Mosher’s ester method. Of these, strobiloscyphone F (6) contains a novel highly oxygenated tetracyclic oxireno-octahydrodibenzofuran ring system. Natural products 1, 6, and 9and the semisynthetic analogue 12derived from 8exhibited cytotoxic activity, whereas 9and 12showed antimicrobial activity. Possible biosynthetic pathways to 1–6, 8, and 9are proposed.

When cultivated under aeroponic growth conditions, Physalis crassifoliaproduced 11 new withanolides (1–11) and seven known withanolides (12–18) including those obtained from the wild-crafted plant. The structures of the new withanolides were elucidated by the application of spectroscopic techniques, and the known withanolides were identified by comparison of their spectroscopic data with those reported. Withanolides 1–11and 16were evaluated for their potential anticancer activity using five tumor cell lines. Of these, the 17β-hydroxy-18-acetoxywithanolides 1, 2, 6, 7, and 16showed potent antiproliferative activity, with some having selectivity for prostate adenocarcinoma (LNCaP and PC-3M) compared to the breast adenocarcinoma (MCF-7), non-small-cell lung cancer (NCI-H460), and CNS glioma (SF-268) cell lines used. The cytotoxicity data obtained for 12–15, 17, and 19have provided additional structure–activity relationship information for the 17β-hydroxy-18-acetoxywithanolides.

Four new ent-kaurane diterpenoids, geopyxins A–D (1–4), were isolated from Geopyxisaff. majalis, a fungus occurring in the lichen Pseudevernia intensa, whereas Geopyxissp. AZ0066 inhabiting the same host afforded two new ent-kaurane diterpenoids, geopyxins E and F (5and 6), together with 1and 3. The structures of 1–6were established on the basis of their spectroscopic data, while the absolute configurations were assigned using modified Mosher’s ester method. Methylation of 1–3, 5, and 6gave their corresponding methyl esters 7–11. On acetylation, 1and 7yielded their corresponding monoacetates 12and 14and diacetates 13and 15. All compounds were evaluated for their cytotoxic and heat-shock induction activities. Compounds 2, 7–10, 12, 14, and 15showed cytotoxic activity in the low micromolar range against all five cancer cell lines tested, but only compounds 7–9, 14, and 15were found to activate the heat-shock response at similar concentrations. From a preliminary structure–activity perspective, the electrophilic α,β-unsaturated ketone carbonyl motif present in all compounds except 6and 11was found to be necessary but not sufficient for both cytotoxicity and heat-shock activation.

Five new isopimarane diterpenes, smardaesidins A–E (1– 5) and two new 20-nor-isopimarane diterpenes, smardaesidins F (6) and G (7), together with sphaeropsidins A (8) and C–F (10–13) were isolated from an endophytic fungal strain, Smardaeasp. AZ0432, occurring in living photosynthetic tissue of the moss Ceratodon purpureus. Of these, smardaesidins B (2) and C (3) were obtained as an inseparable mixture of isomers. Chemical reduction of sphaeropsidin A (8) afforded sphaeropsidin B (9), whereas catalytic hydrogenation of 8yielded 7-O-15,16-tetrahydrosphaeropsidin A (14) and its new derivative, 7-hydroxy-6-oxoisopimara-7-en-20-oic acid (15). The acetylation and diazomethane reaction of sphaeropsidin A (8) afforded two of its known derivatives, 6-O-acetylsphaeropsidin A (16) and 8,14-methylenesphaeropsidin A methyl ester (17), respectively. Methylation of 10yielded sphaeropsidin C methyl ester (18). The planar structures and relative configurations of the new compounds 1–7and 15were elucidated using MS and 1D and 2D NMR experiments, while the absolute configurations of the stereocenters of 4and 6–8were assigned using a modified Mosher’s ester method, CD spectra, and comparison of specific rotation data with literature values. Compounds 1–18were evaluated for their potential anticancer activity using several cancer cell lines and cells derived from normal human primary fibroblasts. Of these, compounds 8, 11, and 16showed significant cytotoxic activity. More importantly, sphaeropsidin A (8) showed cell-type selectivity in the cytotoxicity assay and inhibited migration of metastatic breast adenocarcinoma (MDA-MB-231) cells at subcytotoxic concentrations.