Studies into the total syntheses of various natural products and their derivatives for biological evaluation

Louisa Achini Ho

Research output: ThesisDoctoral Thesis

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Abstract

[Truncated abstract] This thesis describes three projects, all of which are linked by the central theme of palladium-catalysed cross-coupling reactions as key steps in the total syntheses of various natural products and their derivatives for biological evaluation. Chapter 1 provides a brief introduction about natural products as synthetic targets, and the role palladium-catalysed cross-coupling reactions have played in natural product synthesis. Chapter 2 details the total syntheses of Antrodia camphorata natural product maleimide and maleic anhydrides (I, II, and III), in addition to a number of their aryldifferentiated derivatives (e.g. IV and V) using the Negishi and Suzuki cross-coupling reaction protocols as key synthetic steps. The chapter then discusses the ability of these compounds to affect proliferation in non-tumourigenic and tumourigenic liver progenitor cell lines as monitored by the Cellscreen system, a non-destructive rapidscreening instrument. Several derivatives were found to radically slow the proliferation of liver progenitor cells. However, of particular interest were two maleic anhydride derivatives IV and V. These analogues demonstrated selectivity for limiting the proliferation of tumourigenic progenitor cells in comparison with their nontumourigenic counterparts. Chapter 3 describes a formal synthesis for the cyclohexenone epoxide natural product SDEF 678, along with several approaches to the enantioselective total syntheses of SDEF 678 and speciosins A-F. The formal synthesis for the natural product SDEF 678 is based around the use of a Sonogashira cross-coupling, a phenolic oxidation, a Diels– Alder/retro-Diels–Alder sequence, and a diastereoselective epoxidation as key reaction steps. The enantioselective approach to SDEF 678 describes a sequence involving a phenolic oxidation, a Sharpless epoxidation, a Corey-Fuchs reaction, a Sonogashira cross-coupling, and a diastereoselective DIBALH-H reduction as key reaction steps...
Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2013

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