Total synthesis of complex polycyclic natural products using a novel cascade reaction

Alqahtani, Arwa (2023) Total synthesis of complex polycyclic natural products using a novel cascade reaction. PhD thesis, University of Glasgow.

Abstract

The guaianolides comprise a large family of natural products, which includes moroccolide A and micheliolide. The guaianolide natural products contain a 5,7,5 fused tricyclic system. Members of the guaianolide family of natural products have been shown to exhibit potent biological activities following their discovery. Extensive studies have been performed to establish the biomolecular mechanisms responsible for the biological activities of these compounds and assess their potential use as prophylactic and therapeutic agents.

The significant synthetic challenges presented by the guaianolides combined with their biological activities make them interesting targets. There have been numerous syntheses of the structurally related guaianolides family, but to date no total synthesis have been reported for either moroccolide A or micheliolide, due the complexity of their structures, and only a semisynthesis of micheliolide has been attempted. With this in mind, a synthetic strategy has been developed for formation of the 5,7,5 fused tricyclic core of both natural products by application of a reaction sequence developed previously within the Clark group. This involved several key transformations including a ynenone formation, Brønsted acid mediated cyclisation to form furan followed by [3,3]-sigmatropic Cope rearrangement to construct the tricyclic core of both guaianolides.

This thesis presents a synthetic strategy for guaianolide synthesis and progress toward testing the effectiveness of this synthetic strategy for rapid construction of the tricyclic core structures from simple starting materials. After an appropriate model system had been tested, the methodology was to be applied to the synthesis of the natural products micheliolide and moroccolide A. This will be the first attempted total synthesis toward both morocolide A and micheliolide.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Clark, Professor Stephen
• Date of Award: 2023
• Depositing User: Theses Team
• Unique ID: glathesis:2023-83441
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 21 Feb 2023 13:29
• Last Modified: 21 Feb 2023 13:29
• Thesis DOI: 10.5525/gla.thesis.83441
• URI: https://theses.gla.ac.uk/id/eprint/83441