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Improving the Sustainability of Peptide and Polymer Chemistry

Lawrenson, Stefan (2018) Improving the Sustainability of Peptide and Polymer Chemistry. PhD thesis, University of York.

Improving peptide and polymer chemistry Stefan Lawrenson PhD 2018.pdf - Examined Thesis (PDF)
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This thesis explores methods for improving the sustainability of peptide and polymer chemistry, using alternative solvents and bio-based platform molecules. Cyclic carbonates were first investigated as replacements for reprotoxic polar aprotic solvents in peptide chemistry. Using the solution-phase approach several tetrapeptides were first synthesised utilising propylene carbonate as the only reaction solvent. Good to excellent yields were observed in all cases for both coupling (65-91%) and deprotection (80-99%) steps. The use of propylene carbonate for solid-phase peptide synthesis was then demonstrated, through the total synthesis of the natural vasodilator bradykinin in an excellent 77% crude purity. Extending this work, the use of alternative solvents in solid-phase organic synthesis was then explored. The suitability of green solvents for solid-phase organic synthesis was determined by their ability to solvate polymeric supports. In all cases, a solvent was identified that was able to swell a desired resin to 4.0 mL g-1. The outcomes of this investigation were then used to build a computational model of resin swelling using the HSPiP software and verify resin/solvent compatibility through the multicomponent Ugi reaction. The second half of this thesis then explored the ring-opening metathesis polymerisation of amide derivatives of a novel oxanorbornene-lactone. A number of homo- and random co-polymers were prepared, which were found to possess good molecular weights (Mn = 10,763-28,100) and narrow dispersities (Đ = 1.02-1.11). Thermal analysis also revealed the polymers to be amorphous, possessing high thermal degradation (>300 °C) and glass transition (115-203 °C) temperatures. It was also possible to synthesise a block copolymer, but only when the second monomer was added following 80% conversion of the first monomer. Finally, kinetic data showed that the pendant side chains had a minimal influence on propagation rate (2.3×10-3 s-1 - 3.1×10-4 s-1). Finally, the synthesis and application of spirocyclic oxanorbornene-imides were investigated. These monomers were found to be unsuitable for ROMP, but LLAMA analysis showed that the hydrogenated variants were highly promising lead-like compounds. The data suggests they lay perfectly within lead-like space (-1 ≤ cLogP ≤ 3 and Mw = 200-350 Da), are fairly three-dimensional by PMI analysis and had 0% likeness to a random 2% selection of the ZINC database.

Item Type: Thesis (PhD)
Academic Units: The University of York > Chemistry (York)
Depositing User: Mr Stefan Lawrenson
Date Deposited: 23 Nov 2018 16:31
Last Modified: 23 Nov 2018 16:31
URI: http://etheses.whiterose.ac.uk/id/eprint/21397

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