Isolation, synthesis, and biological target identification of natural products from terrestrial and marine environments
department or school: Science, Faculty of
department or school: Chemistry, Department of
data provider: DSpace
degree campus: UBCV
creator: Centko, Ryan Matthew
issued: 2016-02-29T00:00:00Z
issued: 2014
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: 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.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/50064
note: ISOLATION, SYNTHESIS, AND BIOLOGICAL TARGET IDENTIFICATION OF NATURAL PRODUCTS FROM TERRESTRIAL AND MARINE ENVIRONMENTS by RYAN MATTHEW CENTKO B.Sc., The University of South Florida, 2008 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Chemistry) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) August 2014 © Ryan Matthew Centko, 2014 ii Abstract 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 (P…
has type: Thesis/Dissertation
date issued: 2014-09
is shown at: 10.14288/1.0165987
language: eng
degree discipline: Chemistry
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivs 2.5 Canada
rights URI: http://creativecommons.org/licenses/by-nc-nd/2.5/ca/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/50064