Development and analysis of peptide-based catalysts for selective epoxidation and glycosylation reactions.

摘要

Like the muses in Greek mythology, enzymes and other functional molecules found in nature can be sources of inspiration. It is generally accepted that enzymes derive their catalytic properties from their ability to adopt well-defined, three-dimensional structures that allow precisely positioned functional groups to stabilize transition states and facilitate multi-step transformations. Small-molecule catalysts, including many that have been designed to reproduce these qualities of structure and function, can imitate a variety of biological transformations and even perform transformations unknown to Nature. Although chemists have developed a vast number of synthetically useful reactions that allow them to access complex and interesting molecular structures, there remain a number of enzyme-catalyzed processes that chemists cannot yet replicate.;The data presented throughout this thesis describe our efforts to develop and understand short peptides that can catalyze selective epoxidation and glycosylation reactions. Both of these transformations are important biological processes that enzymes can mediated and control.;Chapter 1 describes the development of a catalytic cycle for peracid-based epoxidation and the application of that cycle to a peptide-catalyzed asymmetric epoxidation. Chapter 2 describes a number of experiments designed to study the mechanism by which the catalyst controls the stereochemistry established during this epoxidation. This chapter also details the synthesis of a number of isosteric alkene analogues designed to assess the importance of specific regions of the catalyst. Chapter 3 presents the rational development of an epoxidation catalyst designed to control the regioselective epoxidation of substrates that contain more than one reactive alkene. Chapter 4 discusses structural aspects of the catalytic proline-containing tetrapeptide, its alkene isosteres, simpler proline derivatives, and other proline-containing structures. And finally, Chapter 5 outlines a number of strategies surveyed for approaching catalyst-controlled, regioselective glycosylation.