Cyclic Carbonates from Sugars and Carbon Dioxide: Synthesis, Polymerisation and Biomedical Applications

The biodegradability and when functionalised biocompatibility of aliphatic polycarbonates (APCs) makes them an attractive class of materials for biomedical applications such as tissue engineering scaffolds and drug-delivery carriers. One route to accessing a wide-range of well-defined and functional APCs is the controlled ring-opening polymerisation (ROP) of cyclic carbonates. In turn, these would ideally be prepared by the direct coupling of CO2 with diols to give water as the only by-product. In this way, the combination of CO2 and sugar-derived diols draws upon two natural renewable building blocks for the construction of polycarbonates that are anticipated to show good biocompatibility properties. Chapter 2 develops a simple and mild alternative to the traditional use of phosgene derivatives for the synthesis of six-membered cyclic carbonates from 1,3-diols and CO2. DFT calculations highlighted the need to lower both the CO2-insertion and ring-closing kinetic barriers to cyclic carbonate formation. Organic superbase, 1,8- diazabicyclo[5.4.0]undec-7-ene (DBU) enabled the formation of carbonate species at 1 atm CO2 pressure whereas, the introduction of a leaving group strategy lowered the cyclisation barrier. Mechanistic considerations suggested a kinetic preference for ring- closing via a nucleophilic addition-elimination pathway rather than a SN2-like intramolecular cyclisation. Chapter 3 applies the procedure with CO2 to the preparation of a novel monomer from natural sugar, ᴅ-mannose. ROP was carried out via an organocatalytic approach and a preference for head-tail linkages in the polycarbonate backbone indicated by NMR spectroscopy and supported by DFT calculations. Chapter 4 utilises CO2 to invert the natural stereochemistry of sugars and create a thymidine-based monomer. The thermodynamic parameters of the ROP with 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) catalyst are determined and the properties of the polycarbonates investigated to include preliminary cell attachment studies. Finally, chapter 5 details the synthesis of cyclic carbonates from 2- deoxy-ᴅ-ribose and the investigation into the different ROP behaviour of the α- and β- anomers. The ability to tune the polymer properties through copolymerisation with trimethylene carbonate (TMC) is also discussed.