Synthetic Studies Towards Phorbaketal A

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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. en
dc.publisher ResearchSpace@Auckland en
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 en
dc.type Thesis en
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


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http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/3.0/nz/

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