UC Berkeley

Abstract

Mechanistic Studies of Biomimetic Reactions by Synthetic Enzyme Mimics

By

William Michael Hart-Cooper

Doctor of Philosophy in Chemistry

University of California, Berkeley

Professor Kenneth N. Raymond, Co-chair

Professor Robert G. Bergman, Co-chair

Chapter 1. A brief introduction to common synthetic host structures and justification for the work described herein is provided.

Chapter 2. The development of 1 and related hosts as a new class terpene synthase mimics that catalyze intramolecular Prins cyclizations. The property of water exclusion is observed. Host 1 is also shown to compensate for the gem-disubstituent effect.

Chapter 3. The development of new terephthalamide hosts enabled an investigation of the effect of host structure on the enantio- and diastereoselectivity of these reactions, as well as a simple kinetic analysis. Rate accelerations and turnover numbers are notably high.

Chapter 4. The mechanism of proton transfer in an archetypal enzyme mimic is studied using amide hydrogen deuterium exchange (HDX) kinetics. Collectively, these data shed light on the role of acid, base and water-mediated proton transfer in a synthetic active site with relevance to proton-mediated catalysis. Moreover, the emergent mechanism of solvent-occupied proton transfer raises the prospect of designable hosts with properties that are unique to the integration of their parts

Chapter 5. A short overview is provided, which places the results of chapters 2-4 in context with some broader goals of biomimetic supramolecular chemistry.