The objectives of this proposal are to make creative contributions to the total synthesis of naturally occurring substances possessing clinically significant biological activity. In addition, a number of new reactions are slated for development. The synthesis projects fall into two areas: Antitumor macrolides and polyether antibiotics. The antineoplastic macrolides which will be targets for asymmetric synthesis include both bryostatin and cytovaricin. The two ionophore projects will be concerned with the asymmetric syntheses of ferensimycin-B and lonomycin. New reactions slated for development will include hydroxyl-directed hydrogenations, hydrosilylations, and hydroborations. These reactions should contribute significantly to the development of new concepts and methodology in acyclic stereocontrol.