This research is being funded by the Organic Synthesis Chemistry Program. The synthesis of the complex new substances required by our society in a cost effective manner is the goal of this research. This is a daunting challenge that requires considerable insight and ingenuity to accomplish. Nature is replete with organic compounds of intricate molecular structure. Often these materials may be isolated from their natural sources in quantity; more often they cannot. The alternative to isolation is synthesis--laboratory manufacture from commonly available materials. Although chemists have over the last half-century become rather adept at constructing small amounts of very complicated molecules, they generally cannot prepare most desired organic compounds in an efficient, practical, and cost-effective manner. This 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 inventing new strategies for the laboratory synthesis of complex organic structures. The compounds to be synthesized are molecules of nature--alkaloids and polyisoprenoids. The intent is not just to make a compound, but to do it in a way that will lead to something new about the architectural aspect of molecule-building. The constant goals are: (a) to minimize the required number of tranformations by eschewing protective groups whenever possible, (b) to minimize the required number of transformations by finding ways in which "cascades" of reactions can occur under the same reaction conditions, (c) to simplify the total synthesis process by using, to the extent possible, "low-tech", rather than exotic, expensive reagents. The specific systems to be studied are: petrosin, sarain-A, nominine, aristone, dictyoxetane, velutinal, crinipellin A and members of the daphniphyllum alkaloid family.
