The object of this proposal is to develop viable synthetic routes to the antitumor agents, phyllanthoside and shikodonin. Phyllanthoside exhibits in vivo activity against the P-388 lymphocytic leukemia in mice, and exceptional in vitro cytotoxicity against cells derived from the human carcinoma of the nasopharynx. Our synthetic plan will provide the corresponding aglycone, phyllanthocin, as the naturally occurring antipode. Shikodonin, isoated from dried plant material, exhibits in vitro cytotoxicity and in vivo antitumor activity against Ehrlich ascites carconoma inoculated in mice. Our synthesis relies heavily on new strategies and the development of new methodologies to construct the highly functionalized skeleton.
