Biocatalytic Route to Well-Defined Macromers Built around a Sugar Core

Abstract

By using 4-C-hydroxymethyl-alpha-D-pentofuranose as the sugar core and lipase-catalyzed transformations, a macromer was constructed with exceptional control of substituent placement around the carbohydrate core. The key synthetic transformations performed were as follows: (1) selective lipase-catalyzed acrylation along with prochiral selection of 4-C-hydroxymethyl-1,2-O-isopropylidene-alpha-D-pentofuranose (diastereomeric excess up to 93%); (2) the ring-opening of epsilon-caprolactone, epsilon-CL, from the remaining primary hydroxyl group to give an acryl-sugar capped macromer (M(n) = 11 300, M(w)/M(n) = 1.36, initiator efficiency 50-55%, <5% water initiated PCL chains); (3) selective lipase-catalyzed esterification of the terminal hydroxyl of oligo(epsilon-CL) chains; (4) hydrolysis of the 1,2-O-isopropylidene group at the sugar core without any substantial loss in macromer molecular weight; and (5) homopolymerization of the corresponding macromer. In principle, the method developed is flexible so that it can be used to generate a wide array of unusual macromers and heteroarm stars. In the absence of biocatalytic transformation, such structural control would be extremely difficult or currently impossible to obtain.

Enzymatic Synthesis of Polyesters via Ring-Opening Polymerization

“…For such purposes, the enzymatic method will be effective. Amphiphilic PCL macromonomers were prepared by first using the sugarderived di-to hexahydroxyl group initiators for the regioselective ringopening polymerization of ε-CL, followed by the selective functionalization of the hydroxyl end group of PCL by lipase (Scheme 11a) [102][103][104]. The hydrophilic hydroxyethyl cellulose was grafted by the hydrophobic ε-CL…”

Enantio‐, Regio‐, and Chemoselective Lipase‐Catalyzed Polymer Synthesis

“…Kumar and Gross employed the enzymatic acylation of hydroxyl group using vinyl methacylate, vinyl acetate, and lauric acid as acyl donors and lipase‐catalyzed ring‐opening polymerization of ε‐caprolactone to construct multiple polyester chains on the sugar core ( Figure 6 ). These polymers have been reported to possess the ability to regulate the interactions with lectins, and could be used as pseudoglycoproteins and carriers for drug delivery . Meanwhile, many glucosides or nucleosides have been found to possess antitumor, anti‐inflammation, or other activities, and their regioselecitive acylation could enhance the effectiveness of these drugs .…”

“…[69] These polymers have been reported to possess the ability to regulate the interactions with lectins, and could be used as pseudoglycoproteins and carriers for drug delivery. [69] Meanwhile, many glucosides or nucleosides have been found to possess antitumor, antiinflammation, or other activities, and their regioselecitive acylation could enhance the effectiveness of these drugs. [70,71] Thus, lipase-catalyzed regioselective polymerization to form the oligomer chain on the glucoside will be promising for not only improving the drug efficacy but also constructing polymerdrug conjugates to obtain the controlled or sustainable drug release.…”

An update of biocatalytic selective acylation and deacylation of monosaccharides

“…An example of regioselective enzymatic acylation of a D-ribofuranosic ring was reported by Nascimento and coworkers 82 polymers. 94 Besides, enzymatic acylation of 157a,b was also studied. 95 Additionally, 96,97 diasteroselective deacylation of peracylated furanosides 160a-c (Scheme 26) was accomplished through a butanolysis catalysed by TLL.…”