A new class of 2,5-disubstituted-dioxacycloalkanes were designed and synthesized via stereoselective synthetic method as cancer chemoprevention agents. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model. Some of these compounds exhibited comparable or better anti-inflammatory activities than that of aspirin suggesting that they can be further developed as potential anti-inflammatory drug lead compounds. In addition, treatment of these anti-inflammatory agents did not prolong tail bleeding time in mice. The structure/activity relationships were also analyzed among these compounds.