| Summary: | Chemical investigation of the fermentation extract of the coral-associated fungus <i>Aspergillus</i> sp. ITBBc1 led to the discovery of five unreported <i>p</i>-terphenyl derivatives, sanshamycins A–E (<b>1</b>–<b>5</b>), together with five previously described analogues, terphenyllin (<b>6</b>), 3-hydroxyterphenyllin (<b>7</b>), candidusin A (<b>8</b>), 4,5-dimethoxycandidusin A (<b>9</b>), and candidusin C (<b>10</b>). Their structures were elucidated by HRESIMS data and NMR spectroscopic analysis. Compound <b>1</b> represents the first example of <i>p</i>-terphenyls with an aldehyde substitution on the benzene ring. Compounds <b>2</b>–<b>4</b> feature varying methoxyl and isopentenyl substitutions, while compound <b>5</b> features a five-membered lactone linked to a biphenyl. These findings expand the chemical diversity of the family of <i>p</i>-terphenyl natural products. Compounds <b>1</b>–<b>6</b> and <b>9</b> were evaluated for their inhibitory activity against type 4 phosphodiesterase (PDE4), which is a fascinating drug target for treatment of inflammatory, respiratory, and neurological diseases. Compound <b>3</b> was the most potent and exhibited PDE4D inhibitory activity with an IC<sub>50</sub> value of 5.543 µM.
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