Development of a divergent synthetic strategy for the asbestinins

Campbell, Angus (2019) Development of a divergent synthetic strategy for the asbestinins. PhD thesis, University of Glasgow.

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Abstract

Asbestinins are the most complex of the ether bridged 2,11-cyclised cembranoids, isolated from the gorgonian octocoral species Briareum asbestinum. They have a complex rigid tetracyclic framework with nine or more contiguous stereocentres and a highly substituted tetrahydrofuran, for example in 11-acetoxy-4-deoxyasbestinin D and asbestinin 12. The asbestinins have been shown to possess significant biological activities including antimicrobial and anticancer properties.
The significant synthetic challenge presented by the asbestinins structures combined with their biological activity make them an interesting target for total synthesis. There have been numerous syntheses of the structurally related cladiellin family but only two previous syntheses of the asbestinins which were reported by Crimmins in 2005 and 2008.
Previous work in the Clark group had established methodology for the synthesis of multiple members of the cladiellin family (>10 members synthesised) from a common tricyclic intermediate which could be utilised in the synthesis of the asbestinins. This involved a few key transformations including a tandem oxonium ylide formation, [2,3]-sigmatropic rearrangement to construct the bicyclic core followed by a Stille/Diels–Alder sequence to give a common tricyclic intermediate.
In this thesis, the first total syntheses of five members of the 4-deoxyasbestinin family are reported as well as the second total synthesis of 11 acetoxy 4 deoxyasbestinin D. The syntheses were completed utilising the common tricyclic intermediate previously reported during the synthesis of multiple members of the cladiellin family. The reported total syntheses have allowed for confirmation or re-evaluation of the reported revised structures of members of the asbestinin family.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Total synthesis, asbestinins, natural products.
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Colleges/Schools: College of Science and Engineering > School of Chemistry
Supervisor's Name: Clark, Prof. J. Stephen
Date of Award: 2019
Depositing User: Dr Angus Campbell
Unique ID: glathesis:2019-77897
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 31 Jan 2020 15:54
Last Modified: 05 Mar 2020 22:34
Thesis DOI: 10.5525/gla.thesis.77897
URI: http://theses.gla.ac.uk/id/eprint/77897
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