Functional Lactide Monomers:  Methodology and Polymerization

Abstract

Side-chain-functionalized lactide analogues have been synthesized from commercially available amino acids and polymerized using stannous octoate as a catalyst. The synthetic strategy presented allows for the incorporation of any protected amino acid for the preparation of functionalized diastereomerically pure lactide monomers. The resulting functionalized cyclic monomers can be homopolymerized and copolymerized with lactides and then quantitatively deprotected forming new functional poly(lactide)-based materials. This strategy allows for the introduction of functional groups along a poly(lactide) (PLA) backbone that after deprotection can be viewed as chemical handles for further functionalization of PLA, yielding improved biomaterials for a variety of applications.

Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy

“…Briefly, a biodegradable polylactide derivative with pendant hydroxyl groups (PLA-OH) was prepared via condensation copolymerization of lactic acid and 3-benzyloxy-2-hydroxypropionic acid (2) followed by deprotection of the benzyl groups, as shown in Scheme S1. This hydroxyl-functionalized polylactide can also be prepared by a ring opening copolymerization of lactide and 3-(benzyloxymethyl)-6-methyl-1,4-dioxozone-2,5-dione (3), as previously described (36,37). The pendant functional groups provide a convenient handle for attaching different agents that could be utilized to construct NPs.…”

“…The strategy for the development of drug-functionalized polymers was based on a simple conversion of amino acids to their corresponding α-hydroxy acids (2) (Scheme S1). The first step involved conversion of the amine to a hydroxyl group via diazotization using sodium nitrite in the presence of an acid for 6 h (36,37,46). This high-yielding reaction provided the resultant monomer for direct use in condensation polymerization with lactic acid to give a polylactide copolymer, PLA-OBn (SI Text).…”

“…The condensation polymerization was performed at 150°C for 3 h with a continuous argon purge, followed by a further 3 h under vacuum. The same polymer was prepared using a ring opening polymerization of the cyclic lactide monomer (3), which was made by dehydration of the α-hydroxyl acid under very dilute conditions in toluene with 1% p-toluenesulfonic acid (36,37,46). The benzyl protecting group is necessary for avoiding side reactions of the hydroxyl group during the polymerization.…”

Periodic Incorporation of Pendant Hydroxyl Groups in Repeating Sequence PLGA Copolymers

“…[14][15][16][17][18][19] In the case of PLAs, the typical synthesis of the side-chain bearing polymers is accomplished by the ring-opening polymerization (ROP) of the cyclic lactide monomer with lactide/ glycolide derivatives, esteramides, or N-carboxyanhydrides. [20][21][22][23] These polymerizations, however, produce random copolymers whose microstructure is governed only loosely by the reactivity ratios of the monomers. For some applications the likely non-uniform distribution of the functional groups could interfere with polymer application, e.g., RGD groups added to promote cell adhesion could be concentrated in some areas of a scaffold and absent in others.…”

Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review

“…alcohols, carboxylic acids, amines, acrylates). This procedure provides, for example, functional polyesters or polyurethanes with a defined chemical structure that allow for further modification following polymerization [37]. The second strategy is post-polymerization functionalization, which is the modification of the polymer after the polymerization process [35].…”