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.

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: https://theses.gla.ac.uk/id/eprint/6445