Chemical diversification and anticancer activity of natural products

Natural products have historically formed the backbone of modern drug discovery efforts, particularly for cancer and bacterial infections. Despite this privileged status, difficulties associated with the isolation of new natural products or the de novo synthesis of established natural products, coupled with a growth in high throughput screening, led to a decreased emphasis on natural products for drug discovery during the 1990s. The last decade has brought a renaissance in natural product research in terms of new techniques for isolation, synthesis, and biological characterization and with it a renewed appreciation for the importance of these complex molecules. The chapters herein reflect this interest in natural products as important tools for drug discovery. Chapter 1 highlights the synthetic utility of natural products for the creation of complex small molecules for screening libraries. Chapter 2 details specific work with the natural product gibberellic acid for the synthesis of complex and diverse compounds, and chapter 3 covers the screening of these compounds and the biological characterization of a primary hit, GEM-1. Chapters 4 and 5 focus on the anticancer characterization of two classes of natural products: the epipolythiodiketopiperazines alkaloids and the iridoids prismatomerin and plumericin, respectively. Finally, chapter 6 describes the development of a new analytical method for the cellular analysis of a common target of natural products, the biopolymer tubulin