Dr. Andrew Myers is being given the Presidential Young Investigator Award from the Synthetic Organic Chemistry Program to support his research into the development of new synthetic methodology for biologically active molecules. This work will provide the information required to synthesize the new generation of molecules needed by agriculture and industry. Techniques of chemical synthesis will be developed and applied to the preparation of molecules of biological importance. In the latter category are designed molecules which are accessible only through total synthesis. It is hoped that a deeper understanding of these bioactive substances and their mode of action will be gained through study of their properties, with emphasis on reactivity. One such molecule under study is the antitumor antibiotic neocarzinostatin. Ongoing investigations are aimed at elucidation of the precise mechanism of action of this DNA-damaging agent. Synthetic studies towards the antibiotic as well as analog structures are currently underway. One goal is to utilize the strategic concepts by which neocarzinostatin targets and destroys double stranded DNA in the design of completely non-natural mimics. The highly enfolded and complex antitumor agent Calyculin A represents another target for study. A fundamental goal of this undertaking is the development of reaction methodology of value not only for the synthesis of this antibiotic, but for the preparation of stereochemically complex molecules in general. Again, it is anticipated that through the unique perspective of synthesis/reactivity that valuable insights into the mechanism of action of this substance will be gained. In addition to the methodological studies encompassed by the projects described above, fundamental studies of greater applicability in synthesis are planned. Transformations which represent powerful solutions to widespread and general synthetic problems, such as the preparation of geometrically defined carbon carbon double bonds, are targeted with the goal of devising new and useful solutions.