dc.contributor.advisor |
Brimble, M |
en |
dc.contributor.advisor |
Furkert, D |
en |
dc.contributor.author |
Hubert, Jonathan |
en |
dc.date.accessioned |
2015-01-06T21:50:52Z |
en |
dc.date.issued |
2014 |
en |
dc.identifier.citation |
2014 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/23948 |
en |
dc.description.abstract |
Phorbaketal A (6) is a sesterterpenoid natural product isolated from a Phorbas sea sponge, collected off the coast of Gageo Island, South Korea. 6 is a prototypical member of the structurally related phorbaketal and alotaketal families of natural products, which exhibit a broad range of biological activity including activation of osteoblast differentiation, inhibition of adipogenic differentiation and activation of the cAMP signalling pathway. This thesis describes synthetic endeavours towards phorbaketal A (6), with the view that the methodology established would be applicable to other members of the phorbaketal and alotaketal families. Several synthetic approaches were explored in this work for the construction of the core framework of phorbaketal A (6). Advanced epoxy-spiroketal 181 was identified as a key intermediate for the synthesis of 6. A Hosomi–Sakurai coupling of allylsilane 184 and acetal 185, followed by oxidative cyclisation, was the key focus in endeavours towards spiroketal 181. An alkyne coupling/gold catalysed cyclisation approach from bromide 342 and alkyne 343 was also successfully employed to construct the spiroketal core. Considerable effort was devoted to the preparation of key allylsilane intermediate 184. The attempted synthesis of 184 by derivatising carvone 56 was eventually discontinued in favour of an HWE-based approach, using an unusual benzoyl enol ether phosphonate 325 as a key intermediate. A scalable and efficient synthesis of acetal 185 was established via an intramolecular HWE reaction of phosphonate 190, with the chiral centre established using a Nagao aldol reaction to construct β- hydroxyketone 155. While the final epoxide opening step to form phorbaketal A (6) ultimately proved unsuccessful, these investigations have established a sound platform of synthetic methodology and resulted in the synthesis of key intermediates that will enable further synthetic efforts towards 6 and analogues thereof. |
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dc.publisher |
ResearchSpace@Auckland |
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dc.relation.ispartof |
PhD Thesis - University of Auckland |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ |
en |
dc.title |
Synthetic Studies Towards Phorbaketal A |
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dc.type |
Thesis |
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thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Doctoral |
en |
thesis.degree.name |
PhD |
en |
dc.rights.holder |
Copyright: The Author |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.elements-id |
471837 |
en |
pubs.record-created-at-source-date |
2015-01-07 |
en |
dc.identifier.wikidata |
Q112905644 |
|