Total synthesis of members of the amphidinolide family of natural products

Romiti, Filippo (2015) Total synthesis of members of the amphidinolide family of natural products. PhD thesis, University of Glasgow.

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Abstract

The amphidinolides are macrolide natural products isolated from marine dinoflagellates of the genus Amphidinium and most of them display potent cytotoxic activities in vitro. Amphidinolides C-C3, F and T1-5 represent attractive synthetic targets due to a combination of potent bioactivity and complex molecular architecture.
This thesis describes the total syntheses of amphidinolides T1, T3 and T4, and the preparation of the C1-C17 fragment of amphidinolides C and F.
Concise and high-yielding total syntheses of amphidinolides T1, T3, and T4 have been completed using an alkynyl macrolactone as a common late-stage intermediate. The α-hydroxy ketone motif was installed by sequential alkyne hydrosilylation, epoxidation, and Fleming–Tamao oxidation. A tandem oxonium ylide formation [2,3]-sigmatropic rearrangement reaction was used to construct the trisubstituted tetrahydrofuran core found within the natural products.
The C1-C17 fragment of amphidinolides C, C2, C3 and F was synthesised employing [2,3]-sigmatropic rearrangement of an oxonium ylide generated by decomposition of 1-sulfonyl-triazole to construct the trisubstituted tetrahydrofuran ring found in the natural products. The two main segments were conjoined using a Stille cross-coupling reaction that allowed simultaneous installation of the isomerization-prone 1,3-diene unit.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: total synthesis, amphidinolides, metal carbenoids, [2,3]-sigmatropic rearrangement
Subjects: Q Science > QD Chemistry
Colleges/Schools: College of Science and Engineering > School of Chemistry
Supervisor's Name: Clark, Prof. J. Stephen
Date of Award: 2015
Depositing User: Filippo Romiti
Unique ID: glathesis:2015-6445
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 09 Jun 2015 12:15
Last Modified: 30 Aug 2018 09:51
URI: http://theses.gla.ac.uk/id/eprint/6445

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