Improving the Sustainability of Peptide and Polymer Chemistry

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.