Amino acids are the building blocks of proteins, and thus they, and their chemistry, occupy an important position in biochemistry. Nature is able to efficiently make amino acids in a highly specific fashion because it employs enzymes. However, many amino acids of potential use are not synthesized by nature, and so the chemist is in need of tools to make these compounds with the same specificity as found in nature. This project in the Organic and Macromolecular Chemistry Program is developing such reactions for which the chemistry community will have great use. The overall objective of the proposed research is to develop efficient and practical methodology for the asymmetric synthesis of alpha-amino acids based on carbon-carbon bond constructions of electrophilic glycine-derived templates. In addition, the free radical and electrocyclic couplings to these glycine-templates will be investigated. On the practical side, access to either D- or L- configured amino acids in high optical purity and chemical purity will be the primary utility of this research. These selective coupling reactions will be achieved by a careful study of the fundamental chemistry of hemi-amino acetals as substrates for cationic and radical reactions with a variety of organometallic reagents. A new organotin acetylide coupling reaction has been discovered and will be investigated as a means for preparing vinyl and alkynyl alpha-amino acids which have potent biological activities. Several second-generation chiral auxilliaries will be investigated to broaden the scope of the electrophilic glycine template concept. The new methodology will be demonstrated with total syntheses of several representative, complex amino acids.
