Part I: New catalyst discovery through combinatorial chemistry. Part II: Studies toward the total synthesis of sorangicin A

Methodology for the rapid assessment of potential catalyst libraries was assessed and evaluated in the quest for an acylation catalyst that exhibits both high reactivity and selectivity. Two combinatorial libraries were synthesized based upon a DMAP and an NMI catalytic center. Thermographic screening of each failed to yield useful synthetic lipase structures. The failures and lessons learned from the application of thermography to acylation chemistry was applied to a more general understanding of the use of combinatorial libraries in the search for active catalysts.; Color generation as a means of catalyst detection was applied to the pursuit of a synthetic phosphatase. Screening of a pool of 31,000 potential ligands for a gadolinium metal yielded two ligand structures as active catalysts for the hydrolysis of a naphthol phosphate. Further evaluation and structure studies were performed on two ultimate phosphatase catalysts to garner information on the essential structural motifs of the ligands. The absolute activity of the catalysts discovered was measured and pointed to the high sensitivity of the colorimetric screening performed.; Synthetic application of the reductive aldol transformation was studied in the syntheses of natural products sorangicin A and belachinal. Both structures contain propionate substructures ideal for reductive aldol methodology. Sorangicin A synthesis was highlighted by a highly convergent reaction sequence, with reductive aldol reactions employed to form two of the three main fragments. Belachinal's synthesis was to be a study of intramolecular reductive aldol transformations, but was thwarted by difficulty in accessing appropriate substrates as well as sensitivity in substitution of the acrylate moiety.