Biodegradable Functional Poly(α-hydroxy) Acids: A New Class of Polymers for Pharmaceutical Applications

Abstract

This thesis focuses on the synthesis of functionalized polyesters, poly(α-hydroxy) acids in particular, with increased hydrophilicity as materials for biomedical and pharmaceutical applications. For this purpose, a general synthesis route to functionalized dilactones was designed and optimized. This route made the synthesis of large amounts of functionalized dilactones possible. The obtained dilactones were polymerized (homo- or copolymerized) via ROP to obtain the corresponding functionalized polyesters. Upon deprotection of these polymers, hydroxyl functionalized polyesters were obtained. The obtained polymers are structurally analogous to established polyesters such as PLGA and PLLA. The monomers that were used consisted of either lactic acid or glycolic acid which are endogenous compounds, and (S)-3-(benzyloxy)-2-hydroxypropanoic acid, which is a derivative of serine. Upon deprotection of the latter compound glyceric acid is formed. Glyceric acid can be metabolized in the human body via the glycolytic pathway. It is therefore expected that the degradation products of the polymers used in this study will have a low or absent toxicity. Other polymers that were synthesized contained allyl functional groups. These were oxidized via two different pathways; dihydroxylation and epoxidation. The dihydroxylation gave materials that degraded very rapidly and were therefore not further investigated. The epoxidation, however, gave fully epoxidated polymers which can be used for further functionalization.