Although chemists have become rather adept at constructing small amounts of very complicated molecules, we generally cannot prepare most desired organic compounds in an efficient, practical, and cost-effective manner. Our general inability to conceive and execute practical laboratory syntheses constitutes a frailty of our science. It is the long-term goal of this research to address this deficiency by exploring new strategies for the laboratory synthesis of complex organic structures. The compounds to be synthesized are molecules of Nature--alkaloids, carbohydrates, isoprenoids, and acetogenins. The intent is not just to make compounds, but to do it in a way that will teach us something new about the architectural aspect of molecule-building. Specific synthetic targets are discorhabdin D, sarain A, cylindramide, tricolorin A, the petrosins, and preussomerin A. The fundamental significance of the kind of research being carried out in this project is the improvement of our synthetic abilities. It is for this reason that we identify novel organic structures and strive to discover non-obvious, efficient methods to assemble them from commercially- available building blocks. Our ultimate goal as synthetic chemists is to be able to synthesize any desired organic molecule, no matter how complex, in a manner that would be amenable to commercial production. However, many of the targets we have chosen have intrinsic biological importance, and our synthetic research might have immediate practical importance. Among these target compounds are discorhabdin D, which has activity against solid murine tumors, and preussomerin A, an inhibitor of the important enzyme Ras farnesyl-protein transferase (FTPase). These natural products are so rare that insufficient material is available for full-scale in vivo evaluation. Through total synthesis we hope to remedy this problem.
