Abstract 7-Methoxyflavenes and 5, 7, 8-trimethoxyflavenes were found to undergo stereoselective acid-catalyzed rearrangement to generate the benzopyrano [4, 3-b] benzopyran ring system present in the natural product, dependensin. Dependensin and its analogs were subjected to antimalarial growth inhibition assays against Plasmodium falciparum and found to have IC 50 values ranging between 1.9 and 3.9 μM.