Synthesis and Characterization of Regioselectively Functionalized Mono-Sulfated and -Phosphorylated Anionic Poly-Amido-Saccharides

Abstract

Polysaccharides are abundant in nature and employed in various biomedical applications ranging from scaffolds for tissue engineering to carriers for drug delivery systems. However, drawbacks such as tedious isolation protocols, contamination, batch-to-batch consistency, and lack of compositional control with regards to stereo-and regioselectivity impede the development and utility of polysaccharides, and thus mimetics are highly sought after. We report a synthetic strategy to regioselectively functionalize poly-amido-saccharides with sulfate or phosphate groups using post-polymerization modification reactions. Orthogonally protected β-lactam monomers, synthesized from D-glucal, undergo anionic ring-opening polymerization to yield polymers with degrees of polymerization of 12, 25, and 50. Regioselective deprotection followed by functionalization and global deprotection affords the sulfated and phosphorylated poly-amido-saccharides. The resulting anionic polymers are water soluble and non-cytotoxic and adopt helical conformations. This new methodology provides access to otherwise inaccessible functional polysaccharide mimetics for biomedical applications.

Glycosaminoglycans: What Remains To Be Deciphered?

“…58 59 Phosphorylated glycopolymers with a well-def ined structure have been reported. 60 Conversely, robust, synthetic access to phosphorylated species having the same polysaccharide backbone of natural sulfated GAGs is still lacking, as polysaccharide phosphorylation is a very challenging reaction, requiring rather harsh conditions and generally giving products dif f icult to characterize, with low yields and degrees of derivatization. Therefore, significant advances in this f ield are awaiting.…”

Beyond nylon 6: polyamides via ring opening polymerization of designer lactam monomers for biomedical applications

“…124 While naturally occurring GAGs are widely used as anticoagulants 125 the biological origin of these polysaccharides pose many issues such as contamination, 126 batch-to-batch variation, and structural heterogeneity. 127 Grinstaff et al report glycosaminoglycan-mimicking sulphated polyamides, with regio-selective 128 and non-regioselective functionalization. 129 Using an orthogonally protected glucose based β-lactam monomer (Fig.…”

“…4, 24 ), followed by selective deprotection and sulphation, enables synthesis of varied PAS ( M n 2.36 to 14.1 kDa) with sulphate groups only present on the 6′-hydroxyl position of the glucose repeat unit. 128 Post sulfation of PASs using SO 3 ·NMe 3 affords the non-regio selectively sulphated polymers with an average of one or two sulphates per repeat unit (prepared from monomers 19 and 20 , respectively). 129 The in vitro anticoagulant effect of non-regio selectively sulphated polymers (Fig.…”

Ring‐Opening Polymerization of a Benzyl‐Protected Cyclic Ester towards Functional Aliphatic Polyester†

“…Polymers containing free hydroxyl groups have gained growing interest in biomedical applications. [ 30‐44 ] Hydroxyl groups have significant influence on the solubility and self‐assembly of polymers and can serve as a versatile platform for a broad range of reactions. Thus, the post‐polymerization modification is an essential method for the generation of free hydroxyl groups in polymers due to the high reactivity of hydroxyl groups.…”