Many drugs and other biologically active molecules contain basic nitrogen groups that, in their physiological protonated state - and often constrained into intricate ring systems - contribute to the binding of the agent to its protein target. The major theme of this proposal is to develop new synthetic methods that utilize alkyl azides for the synthesis of cyclic nitrogen containing compounds, and to use those methods for the synthesis of biologically relevant compounds. Work in previous grant periods has resulted in the discovery and examination of three broadly useful reactions (the inter- and intramolecular Schmidt reactions of alkyl azides, and the insertion reaction of hydroxyalkyl azides) and has also demonstrated the utility of the reactions in complex molecule synthesis. We have obtained preliminary data that demonstrates how the Schmidt reaction can be linked with other powerful reactions, such as the Diels-Alder cycloaddition, the aldol condensation, and conjugate addition reactions, to provide one-step syntheses of complex lactams from very simple starting materials. We propose to develop these processes, concentrating on matters of scope, efficiency, and stereoselectivity. These new reactions will also be used to synthesize a variety of alkaloids in biological classes that range from NMDA antagonists to cytotoxic agents. The specific targets proposed include the antitussive agent neostenine, several members of the cylindricine family of natural products, the frog-derived indolizidine 223A, and pinnaic acid.