Beta-amino acids are a prevalent class of biologically active molecules found in medically important natural products ranging from the potent anti-tumor agent paclitaxel (Taxol) to various protease inhibitors. This proposal outlines a novel synthetic approach to structurally diverse members of this important class of compounds. The asymmetric addition of cyanide to achiral aziridines using a peptide-based ligand, Lewis acid catalyst will be developed. The asymmetric addition of cyanide to achiral aziridines using a peptide-based ligand, Lewis acid catalyst will be developed. The resulting chiral beta-amino nitrites will be hydrolyzed to beta-amino acids. Enantioselective cyanide addition to achiral aziridines has never been done; however, the analogous nucleophilic epoxide rang opening with TMSCN is known. The search for chiral catalysts to facilitate highly enantioselective processes has become a priority for organic chemists. The substrate specific chiral catalyst for this reaction will be developed using a combinatorial approach to optimize a modular peptide-based ligand. The other reaction parameters such as solvent, choice of Lewis acid, and cyanide source will be optimized as well. The scope of this new reaction will be investigate by testing a variety of differentially substituted aziridines, the products of which will be hydrolyzed to medically important beta-amino acid derivatives.
