Alpha-Acylamino radical cyclizations are useful for the construction of carbon-carbon bonds adjacent to nitrogen. The importance of this bond construction in alkaloid biosynthesis suggests that the aforementioned cyclizations might be general use in alkaloid synthesis. This proposal describes synthetic routes to three biologically interesting alkaloids using radical cyclization methodology. An enantioselective synthesis of (-)-retronecine is proposed. Esters of this compound, the enantiomer of natural retronecine are of interest as cytotoxic agents. Derivatives of (-)-retronecine will be prepared to evaluate the influence of stereochemistry on biological activity. An enantioselective synthesis of swainsonine, a potent Alpha-mannosidase inhibitor used to develop animal models for human mannosidosis, is also proposed. Analogs will be prepared for evaluation as hexosidase inhibitors. Finally, a total synthesis of the analgesic gelsemine is proposed. This study will, for the first time, make gelsemine substructures available for biological evaluation.
