Six new 6-isopentylsphaeropsidones, strobiloscyphones A-F (<b>1</b>-<b>6</b>), and a new hexadecanoic acid, (2<i>Z</i>,4<i>E</i>,6<i>E</i>)-8,9-dihydroxy-10-oxohexadeca-2,4,6-trienoic acid (<b>7</b>), together with sphaeropsidone (<b>8</b>) and its known synthetic analogue 5-dehydrosphaeropsidone (<b>9</b>) were isolated from <i>Strobiloscypha</i> sp. AZ0266, a fungus inhabiting the leaf litter of Douglas fir (<i>Pseudotsuga menziesii</i>). The structures of <b>1</b>-<b>7</b> were 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 (<b>6</b>) contains a novel highly oxygenated tetracyclic oxireno-octahydrodibenzofuran ring system. Natural products <b>1</b>, <b>6</b>, and <b>9</b> and the semisynthetic analogue <b>12</b> derived from <b>8</b> exhibited cytotoxic activity, whereas <b>9</b> and <b>12</b> showed antimicrobial activity. Possible biosynthetic pathways to <b>1</b>-<b>6</b>, <b>8</b>, and <b>9</b> are proposed.