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

Q Science (General);QD Chemistry

Harkiss, Alexander Hugh ; Engineering and Physical Sciences Research Council (EPSRC) ; Sutherland, Andrew

University:University of Glasgow

Department:School of Chemistry

关键词: Q Science (General);    QD Chemistry;   

Others  :  http://theses.gla.ac.uk/8629/7/2017HarkissPhD.pdf

来源: University of Glasgow

【 摘 要 】

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.