Lipase-catalyzed polymerization, cyclic

Aromatic polyesters were enzymatically synthesized under mild reaction conditions. Divinyl esters of isophthalic acid, terephthalic acid, and p-phen-ylene diacetic acid were polymerized with glycols by lipase CA catalyst to give polyesters containing an aromatic moiety in the main chain.208 In the lipase-catalyzed polymerization of dimethyl isophthalate and 1,6-hexanediol in toluene with nitrogen bubbling, a mixture of linear and cyclic polymers was formed.209 High molecular weight aromatic polyester (Mw 5.5 x 104) was synthesized by the lipase CA-catalyzed polymerization of isophthalic acid and 1,6-hexanediol under vacuum.210 Enzymatic polymerization of divinyl esters and aromatic diols also afforded the aromatic polyesters.211... 

Scheme 11.3 Lipase-catalyzed polymerization of L-tartaric acid derive cyclic carbonate followed by deprotection of the ketal groups to give chiral, hydroxy functional polycarbonate.

Figure 3. Proposed mechanism of the lipase catalyzed polymerization of cyclic oligomers.

Lipase-Catalyzed Polymerization of Dicarboxylic Acids or Their Derivatives. Enzymatic synthesis has been achieved via various combinations of dicarboxylic acid derivatives and glycols. As to the diacid monomer, dicarboxylic acids, activated and nonactivated esters, cyclic acid anhydrides, and polyanhydrides were enzymatically reacted with glycols under mild reaction conditions. 

Polycarbonates have attracted attention in recent years because of their potential use in biomedical applications based on their biodegradability, biocompatibility, low toxicity and good mechanical properties [67]. These polymers can be prepared by the ROP of cyclic carbonate monomers by anionic, cationic, and coordination catalysts. However, lipase-catalyzed polymerization seems to be a feasible alternative to prepare polycarbonates as chemical methods often suffer from partial elimination of carbon dioxide (resulting in ether linkages), require extremely pure monomers and anhydrous conditions. 

Various cyclic esters have been subjected to hpase-catalyzed ring-opening polymerization. Lipase catalyzed the ring-opening polymerization of 4- to 17-membered non-substituted lactones.In 1993, it was first demonstrated that medium-size lactones, 8-valerolactone (8-VL, six-membered) and e-caprolactone (e-CL, seven-membered), were polymerized by lipases derived from Candida cylindracea, Burkholderia cepacia (lipase BC), Pseudomonas fluorescens (lipase PF), and porcine pancreas (PPL). °... 

Lipase-catalyzed synthesis of polyesters from cyclic anhydrides and oxi-ranes was reported. The polymerization took place by PPL catalyst and the molecular weight reached 1 x 10" under the selected reaction conditions. During the polymerizahon, the enzymatically formed acid group from the anhydride may open the oxirane ring to give a glycol, which is then reacted with the anhydride or acid by lipase catalysis, yielding the polyesters. 

The polymerization of dimethyl maleate and 1,6-hexanediol proceeded using lipase CA catalyst in toluene to give the polymer exhibiting exclusively cis structure [55]. During the polymerization, cyclic oligomers were formed. The cycles were semi-crystalline, whereas the linear polymer was amorphous. In the lipase CA-catalyzed copolymerization of dimethyl maleate and dimethyl fumarate with 1,6-hexanediol, the content of the cyclization was found to depend mainly on the configuration and concentration of the monomers [56]. 

Lipase-Catalyzed Ring-Opening Polymerization of Cyclic Monomers... 

Polyester syntheses have been achieved by enzymatic ring-opening polymerization of lactide and lactones with various ring-sizes. Here, we focus not only on these cyclic esters but also other cyclic monomers for lipase-catalyzed ringopening polymerizations. Figure 8 summarizes cyclic monomers for providing polyesters via lipase catalysis. 

Here, lipase-catalyzed ring-opening polymerization of cyclic compounds giving polymers other than polyesters is described. l,3-Dioxan-2-one, six-membered cyclic carbonate, was polymerized in the presence of lipase catalysts (Fig. 13)... 

A second key factor in the lipase-catalyzed ROP of CL is the ability to controi the nature of the endgroups. This has important consequences in preparation of a, (o-functionalized polyesters, which are currently being explored in a variety of applications [111,112]. A systematic study by Heise and coworkers on the initiating efficiency of different initiators (1-3 in Fig. 5) in the CALB-catalyzed ROP of CL showed that three polymeric products were formed cyclic species, water-initiated... 

Besides cyclic esters and carbonates, six-membered cyclic depsipeptides and a five-membered cyclic phosphate were subjected to lipase-catalyzed ring-opening polymerizations, yielding poly (ester amide)s190 and polyphosphate,191 respectively. High temperatures (100—130 °C) were required for the polymerization of the former monomers. 

A degradable triblock copolymer, poly(trimethylene carbonat e)-block-poly[poly(ethylene glycol)-co-cyclic acetal]-Mock-poly(trimethylene carbonate) (PTMC-fe-PECA-b-PTMC), was obtained via chemo-enzymatic approach [118]. The synthesized triblock copolymer consists of a degradable hydrophilic PECA (a,co-glycol synthesized chemically) and an amorphous hydrophobic PTMC (lipase CA-catalyzed polymerization of TMC). 

In an elegant recent work, Loos et al. [51, 52] reported the synthesis of polydialanine) via lipase-catalyzed ring-opening of 2-azetidinone (Scheme 5.4) (see Chapter 14 for details on the polymerization mechanism). After removal of cyclic side products and low-molecular-weight species, pure linear poly(P-alanine) was obtained. The average DP of the polymer obtained was limited to 8 because of the solubility of the polymer in the reaction medium. Control experiments with P-alanine as substrate confirmed that the ring structure of the 2-azetidinone was necessary to obtain the polymer. 

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