Ring-opening polymerization lipase-catalyzed

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 catalysis is often used for enantioselective production of chiral compounds. Lipase induced the enantioselective ring-opening polymerization of racemic lactones. In the lipase-catalyzed polymerization of racemic (3-BL, the enantioselec-tivity was low an enantioselective polymerization of (3-BL occurred by using thermophilic lipase to give (/ )-enriched PHB with 20-37% enantiomeric excess (ee). ... 

Optically active polyesters were synthesized by lipase CA-catalyzed ring-opening polymerization of racemic 4-methyl or ethyl-e-caprolactone. The (5 )-isomer was enantioselectively polymerized to produce the polyester with >95% ee. Quantitative reactivity of 4-substituted e-caprolactone using lipase CA as catalyst was analyzed. The polymerization rate decreased by a factor of 2 upon the introduction of a methyl substitutent at the 4-position. Furthermore, 4-ethyl-8-caprolactone polymerized five times slower than the 4-methyl-8-caprolactone. This reactivity difference is strongly related to the enantioselectivity. Interestingly, lipase CA displayed 5 -selectivity for 4-methyl or ethyl-8-caprolactone, and the enantioselectivity was changed to the (f )-enantiomer in the case of 4-propyl-8-caprolactone. 

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. 

Lipase catalyzed the ring-opening polymerization of medium-size lactones, d-valerolactone (<5-VL, six-membered) and -caprolactone (c-CL, seven-mem-bered). Lipases CC, PF and PPL showed high catalytic activity for the polymerization of <5-VL [74,75]. The molecular weight of the polymer obtained in bulk at 60 °C was relatively low (less than 2000). 

An alcohol could initiate the ring-opening polymerization of lactones by lipase catalyst ( initiator method ). In the lipase CA-catalyzed polymerization of DDL using 2-hydroxyethyl methacrylate as initiator, the methacryloyl group was quantitatively introduced at the polymer terminal, yielding the methacryl-type polyester macromonomer [98]. This methodology was expanded to synthesis of co-alkenyl- and alkynyl-type macromonomers by using 5-hexen-l-ol and 5-hexyn-l-ol as initiator. 

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)... 

S)-Isopropylmorpholine-2,5-dione, six-membered depsipeptide, was polymerized by lipase PC and PPL catalysts [112]. High temperature (100°C or 130°C) was required for the polymerization, yielding biodegradable poly(de-psipeptide). During the polymerization, the racemization of the valine residue took place. Demonstrated was PPL-catalyzed ring-opening polymerization of ethylene isopropyl phosphate, five-membered cyclic phosphate [113]. 

Uyama H, Kobayashi S (1993) Enzymatic ring-opening polymerization of lactones catalyzed by lipase. Chem Lett 1149-1150... 

Feng Y, Kniifermann J, Klee D, Hdcker H (1999) Lipase-catalyzed ring-opening polymerization of 3(S)-isopropylmorpholine-2,5-dione. Macromol Chem Phys 200 1506-1514... 

Conventional ring-opening polymerization of cyclic anhydrides, carbonates, lactones, and lactides require extremely pure monomers and anhydrous conditions as well as metallic catalysts, which must be completely removed before use, particularly for medical applications. To avoid these difficult restrictions, an enzymatic polymerization may be one of the more feasible methods to obtain the polyesters. This method was first reported by two independent groups (Kobayashi [152] and Gutman [153]) who showed that lipases, enzymes capable of catalyzing the hydrolysis of fatty acid esters, can polymerize various medium-sized lactones. 

The aliphatic poly(ether lactonejs are a group of synthetic polymers with high elasticity and high tissue absorptivity [293]. The ether function in the polymer backbone adds flexibility to the ester chain. Ring-opening polymerization of l,4-dioxan-2-one yields an elastic polymer, polydioxanone, with a tensile strength similar to that of human tissue [294]. Polydioxanone has been successfully used to prepare monofilament sutures, with a flexibility superior to that of PGA sutures [294]. Recently, the lipase-catalyzed polymerization of polydioxanone was demonstrated [295]. 

Lipase-catalyzed ring-opening polymerization of nine-membered lactone, 8-octanolide (OL), has been reported.165 Lipases CA and PC showed the high catalytic activity for the polymerization. Racemic fluorinated lactones with a ring size from 10 to 14 were enantioselectively polymerized by lipase CA catalyst to give optically active polyesters.166... 

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. 

Bisht, K.S. Svirkin, Y.Y. Henderson, L.A. Gross, R.A. Kaplan, D.L. Swift, G. Lipase-catalyzed ring-opening polymerization of trimethylene carbonate. Macromolecules 1997, 30 (25), 7735-7742. 

Mei, Y., Kumar, A., and Gross, R.A. (2002) Probing water-temperature relationships for lipase-catalyzed lactone ring-opening polymerizations. Macromolecules, 35.14, 5444-5448. 

Table 4.2 Lipase-catalyzed ring-opening polymerizations.

Scheme 4.18 Lipase-catalyzed ring-opening polymerization of MOHEL.

This chapter provides numerous examples of significant advancements documented in the literature describing cell-free enzyme-catalyzed polymerizations, predominantly using lipases as catalysts. Polymerization reactions occurred by (i) condensations (ii) ring-opening homo- and copolymerizations and (iii) combination of condensation and ring-opening polymerization. 

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. 

Namekawa, S., Suda, S., Uyama, H., and Kobayashi, S. (1999) Lipase-catalyzed ring-opening polymerization of lactones to polyesters and its mechanistic aspects. Int. J. Biol. Macromol., 25 (1-3), 145-151. 

Nobes, G.A.R., Kazalauskas, R.J., and Marchessault, R.H. (1996) Lipase-catalyzed ring-opening polymerization of lactones a novel route to poly(hydroxyalkanoate) s. Macromolecules, 29 (14), 4829-4833. 

Divakar, S. (2004) Porcine pancreas lipase catalyzed ring-opening polymerization of e-caprolactone. J. Macromol. Sci. Part A Pure. Appl. Chem., 41 (5), 537-546. 

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