| Part I. The advent of combinatorial chemistry has provided chemists with the ability to prepare large libraries of chemical compounds. However, only a small segment of the vast number of chemical transformations available to the chemist have been transferred to solid-phase, combinatorial techniques. We have developed a set of criteria for reaction development that has allowed for the translation of chemical methodologies from the solution-phase to the solid-phase. Specifically, the azomethine ylide [3+2] cycloaddition solid-phase methodology has been expanded.; The condensation of primary amino acids to secondary amines and nonenolizable aldehydes in solution provides a number of novel compounds with the general structure 1. This chemistry has been transferred to the solid-phase and a number of representative bicyclic structures have been prepared.*; Part II. The prediction of protein structure has proved an elusive goal for chemists and biochemists. The ability to analyze a protein fragment representative of a particular secondary structural motif has been limited by the inherent instability of delicate hydrogen bonding and hydrophobic interactions in the excised fragment. The α-helix is the most abundant secondary structure found in nature. A small, stable, independent α-helical peptide could elucidate much about protein structure and protein-protein interactions. We have designed a small C-terminal α-helix nucleator, 2. A synthetic route to intermediate 3 is described.*; *Please refer to dissertation for diagrams. |
