Angiogenesis is a complex process involving several distinct and sequential steps such as membrane degradation, migration (chemotaxis), proliferation, and formation of capillary tubes in endothelial cells. Abnormal angiogenesis often occurs in pathological conditions such as cancer, rheumatoid arthritis, diabetic retinopathy, and other chronic inflammatory diseases. An important step in the development of pathological angiogenesis is thought to involve the production of vascular endothelial growth factor (VEGF) by normal and tumor cells, and the subsequent hyperactivation of downstream signaling pathways in endothelial cells. Inhibition of angiogenesis is emerging as a promising strategy for the treatment of angiogenesis-related diseases including cancer. In our screening program to aim at identifying angiogenesis inhibitors of microbial origin, we found novel pentaketide dimers designated as epoxyquinols A (1) and B (2) produced by a filamentous fungal strain isolated from a soil sample. The structures of 1 and 2 were elucidated mainly by NMR experiments including several 2D-NMR methods, X-ray crystallographic analysis, and other spectroscopic analysis. Epoxyquinol A (1) possesses an attractive structure consisting of a highly functionalized cyclohexenone moiety. Moreover, epoxyquinol B (2) is a unique diastereomer of 1 in respect of the structure, biosynthesis, and biological properties. In addition, a related monomer 3 was also identified, which would be a key intermediate of epoxyquinols biosynthesis. The intermolecular Diels-Alder reaction of a corresponding 2H-pyran monomer resulted from 3 via oxidative 6π-electrocyclization is proposed as possible biosynthetic pathways of 1 and 2. Epoxyquinols A (1) and B (2) inhibited VEGF-induced migration in human vein endothelial cells (HUVECs) with the IC_<50> values of 2.8 and 0.8μM, respectively. Further studies on the structure-activity relationships and the biological activities of epoxyquinols are in progress.