Synthesis of rapidly surface eroding polyorthoesters and polyacetals using thiolene click chemistry

Polyorthoesters are generally considered to be highly biocompatible, surface-eroding materials. However, sensitive intermediates and poor mechanical performance have largely prevented their widespread application to date. Herein, a simple and versatile method to synthesize orthoester- and acetal-based polymers is presented. Using 2-methylene-1,3-dioxe-5-pene as a stable bifunctional monomer, sequential highly selective “click” reactions led initially to the formation of orthoesters (OE) in a Markovnikov alcohol addition or acetals via anti-Markovnikov thiol–ene addition. Subsequent photoinitiated thiol addition onto the remaining endocyclic and backbone alkene functionalities lead to thioether formation to produce a class of poly(orthoester-thioether)s or poly(acetal-thioether)s via a step-growth polymerization. While all obtained polymers were found to possess a weight-average molecular weight of above 10 kg·mol^–1, the application of an OE monomer with additional double bond functionality led to a cross-linked polymer network which displayed surface-erosion behavior.