Syntheses of sugar poly(orthoesters) through reverse anomeric effect

Abstract

High molecular weight sugar poly(orthoesters) were synthesized through reverse anomeric effect (RAE). We demonstrated that when RAE-enabled promoters, such as 4-(dimethylamino)pyridine (DMAP), triphenylphosphine (TPP) or imidazole, were employed, efficient polymerizations were achieved, giving sugar poly(orthoesters) with molecular weights up to 18 kDa.

From Glucose to Polymers: A Continuous Chemoenzymatic Process

“…However, the monomer gave the sugar polymer with only moderate molecular weights (M n GPC =4.2 kDa, Figure A). Efforts have been invested, for example, increasing the reaction time/catalyst, even the use of reverse anomeric effect (RAE)‐enabling catalysts such as DMAP (N,N‐dimethylamino pyridine) or TPP (triphenyl phosphine) . Unfortunately, these efforts did not improve the molecular weights, which is possibly due to the low reactivity of the glycosyl chloride (as compared to the glycosyl bromide monomer 3 a , which gave a molecular weight of ca.…”

“…For example, at pH 5, the half‐life of the sugar poly(orthoester) was only 0.6 h, allowing for efficient degradation without the use of toxic reagents or energy input for degradation . However, despite these advantages, the synthesis of the polymer, like every other sugar polymer reported in the literature, was inefficient and tedious, involving many selective protection and deprotection steps in the preparation of a polymerizable monomer …”

A Synthetic Bioinspired Carbohydrate Polymer with Mucoadhesive Properties

“…Alternatively, purely synthetic routes to such polymers are equally challenging as many of the desirable chemical characteristics of polysaccharides for biological applications (pyranose backbone, numerous hydroxyl functionalities, defined stereochemistry) necessitate rigorous and lengthy synthesis to prepare even oligosaccharides (<10 repeating units) . Consequently, efforts are ongoing to develop carbohydrate‐inspired polymers with non O ‐glycosidic linkages such as amide, carbonate, and phosphodiester linkages. These novel materials, however, fail to recapitulate all of the key physicochemical and biointerfacial properties of polysaccharides.…”

“…These novel materials, however, fail to recapitulate all of the key physicochemical and biointerfacial properties of polysaccharides. Indeed, previously reported carbohydrate‐inspired polymers largely suffer from poor aqueous solubility to complete insolubility, a lack of deprotected functional groups important for biological interaction (e.g., hydroxyls, amines, phosphates, carboxylates), and/or rapid degradation in acidic or basic pH . Moreover, the rigid pyranose ring backbone absent in some carbohydrate‐mimic and glyco‐polymers plays an essential role in polymer structure and resulting macroscale properties .…”

A Synthetic Bioinspired Carbohydrate Polymer with Mucoadhesive Properties

“…[14][15][16][17] Alternatively,p urely synthetic routes to such polymers are equally challenging as many of the desirable chemical characteristics of polysaccharides for biological applications (pyranose backbone,n umerous hydroxyl functionalities,d efined stereochemistry) necessitate rigorous and lengthy synthesis to prepare even oligosaccharides (< 10 repeating units). [18][19][20][21][22] Consequently,efforts are ongoing to develop carbohydrate-inspired polymers with non O-glycosidic linkages [23,24] such as amide, [25] carbonate, [26,27] and phosphodiester [28] linkages.T hese novel materials,h owever, fail to recapitulate all of the key physicochemical and biointerfacial properties of polysaccharides.I ndeed, previously reported carbohydrate-inspired polymers largely suffer from poor aqueous solubility to complete insolubility, al ack of deprotected functional groups important for biological interaction (e.g., hydroxyls,a mines,p hosphates, carboxylates), [23,24,[26][27][28] and/or rapid degradation in acidic or basic pH. [23,24,29] Moreover,t he rigid pyranose ring backbone absent in some carbohydrate-mimic [25] and glyco-polymers [30] plays an essential role in polymer structure and resulting macroscale properties.…”