Date of Award

2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Marisa C. Kozlowski

Second Advisor

Gary A. Molander

Abstract

The chaetoglobins are a structurally unique class of azaphilone alkaloid dimers with reported anticancer activity. They are also a potential platform for the development of antibacterial and botulinum antitoxin. Notably, this class of compounds has not been synthesized to date. Chaetoglobin A (1) and B (2) were originally isolated from the endophytic fungus Chaetomium globosum.1 Chaetoglobin A has been shown to be potentially active against human colon and breast cancer. However, the bioactivity of chaetoglobin B has not been studied due lack of material, suggesting the need of further research. The main goal of this project is the design and optimization of a synthetic route for chaetoglobin natural products.

Achiral phenol coupling has been studied for many years; however, the regioselective methods reported to date are substrate-dependent and limited in scope. - Previously, we developed a regio- and enantioselective method for oxidative phenol coupling applying a series of bimetallic and monomeric vanadium catalysts. The aim of this project is to develop a new complementary method for regioselective oxidative phenol coupling. In collaboration with Trung Cao and Young Lee, 84 catalysts were synthesized and screened against a collection of phenolic substrates using High-Throughput Experimentation (HTE). We successfully identified catalysts that give high reactivity toward different substrates, and upon scale-up isolated the products in good yields.

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