Synthesis of novel fluorescent heterocyclic-derived α-amino acids and the total syntheses of piperidine natural products

Harkiss, Alexander Hugh (2017) Synthesis of novel fluorescent heterocyclic-derived α-amino acids and the total syntheses of piperidine natural products. PhD thesis, University of Glasgow.

Abstract

During the course of this PhD, methodology for the synthesis of a series of novel, highly fluorescent pyridine-derived α-amino acids was developed. Enone-derived α-amino acids were subjected to an inverse electron demand hetero-Diels-Alder cycloaddition and aromatisation reaction, which led to a twelve-membered library of pyridine analogues. The optical properties of these compounds were analysed, with several exhibiting interesting fluorescent characteristics. One of the analogues was incorporated into a cell penetrating pentapeptide via solid phase peptide synthesis. The resulting hexapeptide was incubated with human fibroblast cells and fluorescence microscopy was used to show accumulation of the peptide in the cells.

The total syntheses of piperidine containing natural products, spruce alkaloid and (+)-241D were also examined during this PhD. A short nine-step linear sequence was developed giving spruce alkaloid and (+)-241D in 21% and 19% overall yield, respectively. A base mediated 6-endo-trig cyclisation was employed as the key-step followed by stereoselective ketone reduction to complete the total syntheses. The scope of the cyclisation and reduction was examined with a range of enone side-chains resulting in a small library of novel 4-hydroxy-2,6-disubstituted piperidines.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > Q Science (General); Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Funder's Name: Engineering and Physical Sciences Research Council (EPSRC), Engineering and Physical Sciences Research Council (EPSRC), Engineering and Physical Sciences Research Council (EPSRC)
• Supervisor's Name: Sutherland, Dr. Andrew
• Date of Award: 2017
• Depositing User: Mr Alexander H Harkiss
• Unique ID: glathesis:2017-8629
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 05 Jan 2018 11:04
• Last Modified: 19 Jan 2018 10:44
• URI: https://theses.gla.ac.uk/id/eprint/8629