Lipase-catalyzed polycondensation

Polyesters have been obtained in organic medium by polyesterification of hydroxy acids,328,329 hydroxy esters,330 stoichiometric mixtures of diols and diacids,331-333 diols and diesters,334-339 and diols and cyclic anhydrides.340 Lipases have also been reported to catalyze ester-ester interchanges in solution or in die bulk at moderate temperature.341 Since lipases obviously catalyze the reverse reaction (i.e., hydrolysis or alcoholysis of polyester), lipase-catalyzed polyesterifications can be regarded as equilibrium polycondensations taking place in mild conditions (Scheme 2.35). 

Alkyl esters often show low reactivity for lipase-catalyzed transesterifications with alcohols. Therefore, it is difficult to obtain high molecular weight polyesters by lipase-catalyzed polycondensation of dialkyl esters with glycols. The molecular weight greatly improved by polymerization under vacuum to remove the formed alcohols, leading to a shift of equilibrium toward the product polymer the polyester with molecular weight of 2 x 10" was obtained by the lipase MM-catalyzed polymerization of sebacic acid and 1,4-butanediol in diphenyl ether or veratrole under reduced pressure. ... 

Room-temperature ionic liquids have received much attention as green designer solvents. We first demonstrated that ionic liquids acted as good medium for lipase-catalyzed production of polyesters. The polycondensation of diethyl adipate and 1,4-butanediol using lipase CA as catalyst efficiently proceeded in l-butyl-3-methylimidazolinium tetrafluoroborate or hexafluorophosphate under reduced pressure. The polymerization of diethyl sebacate and 1,4-butanediol in l-butyl-3-methylimidazolinium hexafluorophosphate took place even at room temperature in the presence of lipase BC. ... 

Lipase-Catalyzed Polycondensation of Oxyacids and their Esters 243... 

Unactivated esters, typically alkyl esters, often show low reactivity toward lipase catalyst for transesterifications. In the case of the lipase-catalyzed polycondensation of dialkyl esters with glycols, the polymer of high molecular weight was not obtained. The molecular weight improved when vacuum conditions were used Mw reached more than 2 x 104 in the combination of diethyl sebacate and 1,4-butanediol catalyzed by lipase MM [30]. 

Mahapatro, A., Kalra, B Kumar, A. and Gross, R. A., Lipase-catalyzed polycondensations effect of substrates and solvent on chain formation, dispersity, and end-group structure. Biomacromolecules, 2003, 4, 544. 

Fig. 12 Lipase-catalyzed polycondensation of 1,6-hexanedithiol with dicarboxylic acid diesters to give polythioesters [43]...

Lipase-catalyzed polycondensation and transesterification reactions are the subjects of intensive research activities but polyesters of low molecular weight are obtained by this technique [45-52]. 

Lactonization and Polycondensation. The lipase-catalyzed intramolecular transesterification of a range of w-hydroxy esters has been investigated extensively - and was observed to be very dependent on the chain length of the substrate (eq 16). 

All-trans unsaturated ester oligomers have been synthesized by lipase-catalyzed polymerization of diesters of fumaric acid and 1,4-butanediol.217 No isomerization of the double bond was observed, as opposed to the extensive isomerization found during chemical polycondensations. Crystallinity was found in the enzymatically formed unsaturated oligoesters prepared in acetonitrile, whereas industrial unsaturated polyesters are amorphous. 

Polycarbonate synthesis by lipase-catalyzed polycondensation was demonstrated. Activated dicarbonate, 1,3-propanediol divinyl dicarbonate, was used as the monomer for enzymatic synthesis of polycarbonates.222 Lipase CA-catalyzed polymerization with a,co-alkylene glycols produced the polycarbonates with Mw up to 8.5 x 103. Aromatic polycarbonates with DP larger than 20 were enzymatically obtained from the activated dicarbonate and xylylene glycols in bulk.211... 

Scheme 4.8 Lipase-catalyzed polycondensation of unsaturated (a) and epoxidized (b) dicarboxylic acids with diols.

Lipase-catalyzed synthesis of polyesters came to the focus after two major breakthroughs in 1984, novel lipase-catalyzed polycondensation to give oli-goesters in 1993, discovery of the catalysis for ring-opening polymerization of lactones. 

S. (2005) Preparation of aliphatic poly(thioester) by the lipase-catalyzed direct polycondensation of... 

Uyama, H., Inaka, K., and Kobayashi, S. (2000) Lipase-catalyzed synthesis of aliphatic polyesters by polycondensation of dicarboxylic acids and glycols in solvent-free system. Polym. J., 32 (5), 440-443. 

Warwel, S., Demes, C., and Steinke, G. (2001) Polyesters by lipase-catalyzed polycondensation of unsaturated and epoxidized long-chain a,co-dicarboxylic acid methyl esters with diols. J. Polym. Sci. Part A Polym. Chem., 39 (10), 1601-1609. 

Also in 2005 Kong et al. [49] filed a patent application on a process for preparing an aqueous polyamide dispersion by lipase-catalyzed polycondensation of a diamine and a dicarboxylic acid in aqueous medium. In a separate patent application [50], they reported the process for preparing an aqueous polyamide dispersion by lipase-catalyzed reaction of an aminocarboxylic acid compound in aqueous medium. 

Lipase-catalyzed synthesis of aliphatic polyesters via diacid/diol polycondensation reactions have been explored by us and others at temperatures of 90°C and below (4,5). The substrates used in previous studies are a,a)-linear aliphatic diacid and/or diol monomers with six or more carbons. Herein we report a new method that allowed the first lipase-catalyzed synthesis of high molecular weight PBS fi om practical monomer precursors. 

Polymer Production. The high selectivity of enzymes allows the production of polymers with high chemical, regio- or stereoselectivity (61-63). Polyesters can be obtained through lipase-catalyzed polycondensation of hydroxyacids or of diols with diacids, as shown in Figure 12. Lipases can also catalyze the ringopening polymerization of lactones of various ring sizes. Lipases can also be used to produce monomers, difficult to obtain chemically, that are then polymerized. For instance, various monosaccharides were esterified with vinyl acrylate. 

There is, of course, an equilibrium between the monomers and polymer in the lipase-catalyzed polycondensation of dialkyl esters and glycols. In the lipase CC- or MM-catalyzed polymerization of dimethyl succinate and 1,6-hexanediol in toluene, adsorption of methanol by molecular sieves or elimination of methanol by nitrogen bubbling shifted the thermodynamic equilibrium (101). When dicar-boxy lie acid dialkyl esters and a , >-alkylene glycols were used as monomers, cyclic oligomers were formed from any monomer combinations examined (102). The yield of the cyclics depended on the monomer structure, initial concentration of the monomers, and reaction temperature. The ring-chain equilibrium was observed and the molar distribution of the cyclic species obeyed the Jacobson-Stockmayer equation. 

Fig. 6. Lipase-catalyzed polycondensation of divinyl esters and glycols.

Ester copolymers were synthesized by lipase-catalyzed copol5mierization of lactones, divinyl esters, and glycols (177). The nmr analysis showed that the resulting product was not a mixture of homopolymers, but a copolymer derived from the monomers, indicating that two different modes of pol5mierization, ringopening polymerization and polycondensation, simultaneously take place through enzyme catalysis in one pot to produce ester copolymers. 

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