Marine organisms are taxonomically diverse yet unique, hence they are considered as a reservoir of potential bioactive secondary metabolites. Many of these marine secondary metabolites have already been successfully developed for medicinal usages. In our ongoing study to search new antimicrobial agents from marine resources by the established bioassays of antimicrobial and anti-biofilm formation activities , we have screened 65 crude extracts from marine invertebrates and marine-derived microbes toward Staphylococcus aureus. Among them, the extract of Trichroderma reesi showed apparent inhibitory effect against S. aureus by punch and paper disc plate tests. Furthermore, by the bioassay-guided fractionation isolation, a series of bioactive compounds, including 6-n-pentyl-α-pyrone, as well as a series of peptaibols, were isolated. We tried to synthesize a series analogues of 6-n-pentyl-α-pyrone and evaluate their anti-microbial and anti-biofilm formation activities against S. aureus. In the poster, the structure-activity relationship of this type of compounds will be presented.