Novel one-pot methods for the synthesis of fluorescent amino acids

McGrory, Rochelle (2023) Novel one-pot methods for the synthesis of fluorescent amino acids. PhD thesis, University of Glasgow.

Abstract

The aim of this PhD was to utilise novel methodology for the synthesis of fluorescent amino acids. The first section describes the development of a mild, one-pot diazotisation and cyclisation procedure for the synthesis of benzotriazinones and benzothiatriazinedioxides via stable aryl diazonium tosylates. The synthetic utility of the procedure was highlighted by the generation of various biologically active compounds containing these heterocycles. The second section discusses incorporation of these heterocyclic scaffolds into the side-chains of amino acids. This generated a range of novel fluorescent amino acids with dual emission properties. The amino acid with optimal fluorescent properties was incorporated into a cell-penetrating peptide using solid phase peptide synthesis and investigated for use as a biological imaging agent.

The third project focused on the synthesis of stilbene and biphenyl amino acids via short synthetic routes. Synthesis of the stilbene series was achieved via diazotisation of a protected 4-aminophenyalanine analogue followed by a Heck-Matsuda cross-coupling reaction. The biphenyl amino acids were synthesised utilising a novel one-pot nonaflate formation and Suzuki-Miyaura cross coupling reaction. The optical properties of both series were investigated.

The final section discusses functionalisation of tyrosine via a mild Suzuki-Miyaura cross-coupling reaction. This generated a library of novel amino acids with interesting fluorescent properties. It was found that a significant improvement in the brightness of this series could be achieved via a C–H bond activated cyclisation to give the corresponding dibenzofuran.

• 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: Sutherland, Professor Andrew
• Date of Award: 2023
• Depositing User: Theses Team
• Unique ID: glathesis:2023-83728
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Jul 2023 09:26
• Last Modified: 19 Jul 2023 09:29
• Thesis DOI: 10.5525/gla.thesis.83728
• URI: https://theses.gla.ac.uk/id/eprint/83728

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