Date of Award

2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Madeleine M. Joullié

Abstract

Since the discovery and isolation of the didemnin family of marine depsipeptides in 1981, the synthesis and biological activity of its congeners have been of great interest to the scientific community. Of those, didemnin B was the first marine natural product to reach phase II clinical trials, stimulating many analogue syntheses to date. Almost two decades later, tamandarins A and B were reported and found to possess a structure similar to that of the didemnins. Significant efforts have been devoted to the syntheses of tamandarin analogues to find whether they behaved as didemnin mimics or as individual therapeutic agents. The biological and synthetic significance of the didemnins, tamandarins, and related natural products are discussed in Chapter 1.

The improved second-generation synthesis of the tamandarin B macrocycle and its successful application to the syntheses of three novel tamandarin B side chain analogues are presented in Chapter 2. The results of these investigations could help elucidate the structure-activity relationship as well as mode of action of these natural products.

Chapter 3 deals with the generation of structurally intriguing azabicyclic [3.1.0]- and [4.1.0]aminocyclopropanes and their application in an unprecedented ring-opening conditions to afford corresponding 3-piperidinone and 3-azepinone derivatives which are important pharmaceutical motifs.

Chapter 4 introduces a rapidly growing family of natural diketopiperazine alkaloids: epipolythiodiketopiperazine (ETP) alkaloids, and related synthetic efforts in the generation of these alkaloids. Extensive synthetic investigation towards the formal synthesis of (−)-epicoccin G and other related epidithiodiketopiperazine alkaloids have been conducted. A novel methodology to access the 6-5-6-5-6 pentacyclic framework present in many ETP alkaloids is presented. Further application of this methodology in total synthesis could provide ETP alkaloids that have not been synthesized.

Chapter 5 deals with the development and successful application of 1,2-indanedione functionalized gold nanoparticles in a modified multi-metal deposition process for the development of latent fingerprints on paper. Although a wide variety of ninhydrin-like compounds have been developed as chemical agents for this process over the years, considerable portions of latent fingerprints still escape detection. The new approach provides an alternative method of fingerprint detection that could be utilized in challenging situations.

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