The proposed research involves the development of new methods for the synthesis of complex organic molecules and the application of these methods to the total synthesis of biologically important natural products and hormones. The first section involves new methods for the synthesis of nitrogen containing heterocycles. We wish to employ vinylimidates and N-acyl vinyl imidates as 4 pi and 2 pi electron components in the intramolecular Diels-Alder reaction. These new methods afford the potential for enantiospecific construction of perhydroisoquinoline and perhydroisoindole ring systems, common substructural features of many biologically important alkaloids. The second section describes new methodology for ring annulation chemistry. Utilizing a novel class of synthetic intermediates, bridgehead enol lactones, we are developing general protocols for controlling both regio- and stereochemistry in Diels-Alder reactions. These methods are amenable to the enantiospecific synthesis of the steroid ring nucleus. Particular emphasis will be focused on developing a short, enantiospecific entry into the adrenyl corticoids. The third section outlines our program in the synthesis of taxane natural products. We have developed a short convergent entry into the taxane skeleton and our targets for the immediate future include compounds that we will screen as protomers for microtubule formation.
