Substituted glycolides from natural sources: Preparation, alcoholysis and polymerization

Polylactides, polyglycolides and copolymers containing both glycolate and lactate fragments are biocompatible and biodegradable materials that can be used for environmentally friendly packaging, 3D printing, surgery, drug delivery and other applications. Here we present a first comparative study of a series of 1,4-dioxan-2,5-diones (glycolides: MeGL, iPrGL, iBuGL, BnGL, PhGL and MePhGL) that can be synthesized from natural L-α-hydroxy acids or L-α-amino acids. The formation of (R,R)(S,S)-MePhGL was confirmed by X-ray diffractometry and explained using density functional theory (DFT). We found that diester fragments are retained during the non-catalytic methanolysis of these compounds and that ring-opening regoiselectivity depends on the bulkiness of the substituents. Ring-opening polymerization, catalyzed by 1,5,7-triazabicyclo[4.4.0]undec-5-ene, yielded alkyl-substituted polyglycolides with given MWs. Controlled polymerization of PhGL was possible at low monomer/initiator ratios, while (R,R)/(S,S)-MePhGL formed oligomers and epimerized products. DFT modeling provided an explanation for the observed patterns based on the ease of enolization and the stability of the enolate-anions of phenyl-substituted glycolides. Solutions of MeGL, iPrGL, iBuGL, BnGL and PhGL homopolymers in hexafluoroisopropanol were electrospun into fibrous mats whose morphologies, mechanical characteristics, biodegradabilities and thermal properties varied widely and depended on the substituents on the glycolide.