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Type: Theses
Title: Biomimetic synthesis of marine sponge derived natural products
Author: Kuan, Kevin Kar Weng
Issue Date: 2016
School/Discipline: School of Physical Sciences
Abstract: There is a longstanding interest in the total synthesis of meroterpenoid natural products. These secondary metabolites of marine sponge origin not only display interesting biological activity, but also possess an intriguing molecular architecture, and thus have emerged as appealing targets for total synthesis. Herein this thesis, we report the synthesis of several marine natural products starting from (+)-sclareolide, a cheap and commercially available chiral pool starting material. A brief account on the recent applications of (+)-sclareolide in the field of total synthesis is first described in chapter one. An improved total synthesis of (+)-liphagal is reported in chapter two. The key intermediate can be obtained from (+)-sclareolide in just 10 steps. The construction of the 6,7,5,6-tetracyclic framework was achieved via a pinacol ring expansion methodology, followed by formation of the hemiacetal, and subsequent dehydration to form the benzofuran moiety. Alternatively, this ring expansion can also proceed from the ortho-quinone methide generated in-situ under acidic conditions. Furthermore, the feasibility of a biomimetic conversion of (+)-siphonodictyal B, a co-isolated natural product, to (+)-liphagal was also investigated using a simplified model system. While the results from the model study proved to be encouraging, the formation of a stable ortho-quinone methide was observed while attempting this one-pot epoxidation-ring expansion approach. The preparation of (+)-aureol from (+)-sclareolide is described in chapter three. Key transformations include a series of bioinspired stereospecific [1,2]-hydride and methyl shifts to form the aureane skeleton, and a late stage biomimetic cycloetherification reaction under acidic conditions to afford the desired natural product. In addition, simple modification of the cycloetherification reaction produced a novel tetracyclic molecule with an unprecedented seven-membered cycloether ring. Finally, recent progress towards frondosin A is described in chapter four. While a convergent strategy approach utilising the key intermediate in chapter three failed to deliver the target molecule, a structural isomer of the natural product could be obtained from a novel ring expansion cascade. This sequence involved a dehydration, ring expansion, di-TBS deprotection, and cycloether formation in a one-pot operation. Preliminary attempts to convert this structural isomer to frondosin A or its quinone derivative are reported.
Advisor: George, Jonathan
Sumby, Christopher James
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, School of Physical Sciences, 2016.
Keywords: biomimetic chemistry
organic chemistry
total synthesis
natural product synthesis
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at:
DOI: 10.4225/55/5b2096ee98bb0
Appears in Collections:Research Theses

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