UBC Theses and Dissertations

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UBC Theses and Dissertations

Isolation, synthesis, and biological target identification of natural products from terrestrial and marine environments Centko, Ryan Matthew


Natural products offer an unparalleled resource for the discovery and development of chemical tools to be used by humans. The terrestrial and marine environments contain unique niches where organisms chemically adapt to produce compounds that have proven useful medicinally and beyond. In the following chapters, several classes of novel natural products from terrestrial fungi and marine sponges will be presented. In some cases, synthetic methodology, biological activity and enzymatic target identification will also be presented. Chapters 2 and 3 highlight ramariolides A–D (2.18–2.21) and dhilirolides A–N (3.9–3.22), two new fungal derived compound classes isolated from terrestrial sources. The structure elucidation of these compounds will be presented alongside their biological activities as antimycobacterial and insecticidal agents, respectively. Chapter 4 contains the structure elucidation of three new members of the xestoquinone family of compounds, xestolactone A (4.19), xestosaprol O (4.20), and xestosaprol P (4.21) along with their potent inhibitory effect on human indolamine 2, 3-dioxygenase (hIDO). A new method for synthetic access to derivatives of these compounds is demonstrated in Chapter 5 along with a brief structure activity relationship (SAR) study. Lastly, Chapter 6 discusses latonduine A (6.9), a sponge-derived alkaloid, which has shown promise as a lead structure for the correction of cystic fibrosis (CF). Probes derived from latonduine A (6.9) have led to identification of poly (ADP-ribose) polymerase (PARP) as the enzymatic target. Methodology for the probes’ construction and SAR studies resulting in simplified synthetic analogues of latonduine will be presented.

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