The highly oxygenated diterpenes tripdiolide and triptolide exhibit significant activity against a number of anticancer screens. Tripdiolide is regarded as a very strong candidate for clinical evaluation, but only limited amounts of material are available from the natural source. The objective of this project is the stereocontrolled total synthesis of these synthetically challenging substances. During the course of this effort a large number of analogs of tripdiolide will also be prepared and submitted to the National Cancer Institute for evaluation as possible cancer chemotherapeutic agents.