The trioxacarcins comprise a new class of DNA-modifying natural products with potent antiproliferative effects. Fewer than a dozen trioxacarcins have been identified to date. We recently completed the first synthesis of a trioxacarcin, DC-45-A2, using a highly modular, convergent route to a differentially protected precursor that should serve as a highly diversifiable platform for the future synthesis of trioxacarcins. We envision that this key intermediate can easily be modified to produce hundreds of non-natural trioxacarcins, if not more. We also plan to target natural trioxacarcins, including trioxacarcin A, and will evaluate all of the compounds we synthesize in panels of cultured human cancer cells.