A　new　polyketide:　3R,　5R-(-)-talaroflavone　(2),　along　with　15　known　compounds　were　isolated　from　a　EtOAc　extract　of　a　sponge-derived　fungus　Alternaria　sp.　F49.　Compounds　1-2　and　3-4　were　separated　as　two　pairs　of　enantiomers　by　chiral　HPLC　from　I　and　II.　The　structures　of　compounds　1-16　were　elucidated　by　means　of　NMR　and　MS.　Furthermore,　the　absolute　configurations　of　compounds　1-2　were　determined　by　single　crystal　X-ray　diffraction　experiment　and　CD　analyses.　Compounds　6,　8-10　were　isolated　from　this　genus　(Alternaria　sp.)　for　the　first　time.　Compound　16　showed　moderate　COX-2　enzyme　inhibitory　activity　with　IC50　of　7.3　μmol　·　L-1.　©　2018　Zhonghua　Yixuehui　Zazhishe.　All　rights　reserved.