This research will be funded under the Organic and Macromolecular Chemistry Program. The synthesis of the complex molecules that are found in nature requires the development of highly sophisticated new synthetic reactions. The work to be done in this research will develop new ways of making carbon-carbon bonds which are connected to one another in a right- or left-handed sense. This work could greatly increase our ability to make important substances for medicine and agriculture. The principal focus of this research program will continue to be the discovery and development of new stereoselective reactions. Among the objectives for continued study will be the development of several new families of chiral acylating agents, the exploration of new asymmetric acylation and carboxylation reactions of chiral enolates, and new aldol reaction concepts. In addition, the development of effective chiral sulfinyl transfer reagents will continue, as will the deelopment of several new families of chiral bases and nucleophiles. These latter reagents will be employed in kinetic resolution reactions. In particular, it is intended to develop a protocol for the "deracemization" of racemic alpha-amino acids; that is, the kinetic resolution of an amino acid derivative under conditions of continous reactant racemization. Also, it is intended to synthesize a series of chiral octahedral complexes of Cr(III), Ce(III), Ln(III, Mo(IV) and Mo(VI) and explore the utility of these chiral reagents in a number of useful reactions. For example, the Cr(III), Ce(III), Ln(III) complexes appear to be attractive for the stereoselective delivery of chiral nucleophiles and organometals while the Mo(IV) and Mo(VI) complexes are anticipated to be useful in asymmetric oxo-transfer reactions. Finally, it is intended to complete the synthesis of the macrolide erythronolide B and attempt the asymmetric synthesis of the immunosuppressive macrolide FK-506.
