| Summary: | Four new compounds were isolated from the Vietnamese marine sediment-derived fungus <i>Aspergillus flocculosus</i>, one aspyrone-related polyketide aspilactonol G (<b>2</b>), one meroterpenoid 12-epi-aspertetranone D (<b>4</b>), two drimane derivatives (<b>7</b>,<b>9</b>), together with five known metabolites (<b>1</b>,<b>3</b>,<b>5</b>,<b>6</b>,<b>8</b>,<b>10</b>). The structures of compounds <b>1</b>–<b>10</b> were established by NMR and MS techniques. The absolute stereoconfigurations of compounds <b>1</b> and <b>2</b> were determined by a modified Mosher’s method. The absolute configurations of compounds <b>4</b> and <b>7</b> were established by a combination of analysis of ROESY data and coupling constants as well as biogenetic considerations. Compounds <b>7</b> and <b>8</b> exhibited cytotoxic activity toward human prostate cancer 22Rv1, human breast cancer MCF-7, and murine neuroblastoma Neuro-2a cells.
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