New synthetic approaches to prepare degradable polymers

This thesis is concerned with the synthesis of acid labile co-polymers. Two polymer systems were examined (1) polyacetals and (2) poly(ortho esters). As for poly(ortho esters), there is a need for better synthetic methods to prepare these polymers more easily without the need of stringent anhydrous conditions, with more broad structural variation, and in a more cost effective manner. Pendent functionalised polyacetals derived from PEG and tyrosine derived monomer diols have been prepared and their structure activity relationships determined. A smaller size alkyl chain on the tyrosine derived monomer diol increased the rate of degradation of these polyacetal libraries. For poly (ortho esters), a first strategy involved the preparation of novel stable orthoester monomers. The key aspect was to embed the orthoester within the monomer while providing orthogonal polymerisation functionality. This synthetic route attempts to address the synthetic limitations for the preparation of existing poly(ortho esters) and it is believed to be the first such example. The stabile symmetrical bicyclic [2 .2 .2 ] orthoester monomer molecule derived from the naturally occurring metabolite phenyl acetic acid was used to prepare the new poly(ortho esters). The bicyclic orthoester [2.2.2] ring arrangement provided the monomer with rigidity, therefore enabling a pure solid monomer to be prepared in three synthetic steps. This approach provided a more efficient polymerisation reaction that requires less stringent polymerisation reaction conditions then existing literature examples for preparing poly(ortho esters). The second broad strategy examined the synthesis of a hydrolytically stable precursor poly (oxetane esters), which underwent a pH triggered rearrangement reaction within the polymer mainchain to prepare orthoester moieties in the polymer mainchain. In conclusion these strategies have provided new synthetic examples of preparing the highly degradable acid labile polymers e.g. poly(ortho esters). This thesis is dedicated to my father.