Poly lipase-catalyzed

Poly(malic acid) is a biodegradable and bioadsorbable water-soluble polyester having a carboxylic acid in the side chain. The chemoenzymatic synthesis of poly(malic acid) was achieved by the lipase-catalyzed polymerization of benzyl (3-malolactonate, followed by the debenzylation. The molecular weight of poly(benzyl (3-malolactonate) increased on copolymerizafion with a small amount of (3-PL using lipase CR catalyst. ... 

In 1985, a lipase-catalyzed polymerization of 10-hydroxydecanoic acid was reported. The monomer was polymerized in benzene using poly(ethylene glycol) (PEG)-modified lipase soluble in the medium [12]. The degree of polymerization (DP) of the product was more than 5. PEG-modified esterase from hog Ever and lipase from Aspergillus niger (lipase A) induced the oligomerization of glycolic acid [13]. 

Chemoenzymatic synthesis of biodegradable poly(malic acid) was performed by lipase-catalyzed polymerization of benzyl /J-malolactone, followed by the debenzylation [72]. The addition of a small amount of /J-PL (17 mol % for the monomer) increased Mw up to 3 x 104 [73]. 

It should be mentioned that when a hexa(hydroxyl) initiator is used for the lipase catalyzed polymerization of s-CL, only one hydroxy function is active [100]. This leaves five remaining OH groups for polymerization of new or another monomers. Comb poly(e-CL)s have also been prepared [101, 102] starting from a copolymer of e-CL and 5-ethylene ketal-e-caprolactone as shown below ... 

Feng Y, Klee D, Keul H, Hdcker H (2000) Lipase-catalyzed ring-opening polymerization of morpholine-2,5-dione derivatives a novel route to the synthesis of poly(ester amide)s. Macromol Chem Phys 201 2670-2675... 

Ester synthesis of fatty acid ethyl ester. The lipase-catalyzed esterification of fatty acid and alcohol is well-known. It was also favorable for the esterification of poly unsaturated fatty acids under mild conditions with the enzyme. However, the activity of native lipase is lower in polar organic solvents, i.e. ethanol and methanol. The synthesis of Ae fatty acid ethyl ester was carried out in ethanol using the palmitic acid-modified lipase. As shown in Figure 7, the reactivity of the modified lipase in this system was much higher than that of the unmoditied lipase. 

Moreover, lipase-catalyzed reactions of linear and cyclic poly(3-hydroxy-butanoates) were subjected to hydrolysis, transesterification, and intramolecular esterification. A cyclic polymer along with linear polymers was pro-... 

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]. 

Scheme 4. Lipase-catalyzed ring-opening polymerization of trimethylene carbonate to linear poly(trimethylene carbonate) [18].

The lipase-catalyzed copolymerization of lactones often afforded random copolyesters, despite the different enzymatic polymerizability of lactones in some cases.165 167g-174 So far, the random copolymers were enzymatically obtained from combinations of d-VL-e-CL, e-CL-OL, e-CL-PDL, and OL-DDL. The formation of the random copolymers suggests that the intermolecular transesterifications of the polyesters frequently took place during the copolymerization. By utilizing this specific lipase catalysis, random ester copolymers were synthesized by the lipase-catalyzed polymerization of macrolides in the presence of poly-(e-CL).175... 

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. 

Matsumura, S. Tsukada, K. Toshima, K. Novel lipase-catalyzed ring-opening copolymerization of lactide and trimethylene carbonate forming poly(ester carbonate)s. Int. J. Biol. Macromol. 1999, 25 (1-3), 161-167. 

Hayes, D.G. Lipase-catalyzed synthesis of poly-hydric alcohol-poly(ricinoleic acid) ester star polymers. Polym. Prepr. (Am. Chem. Soc., Div. Polym. Chem.) 2005, 46 (1), 276-277. 

The enzymatic polymerization of methyl ricinoleate was performed using an immobilized lipase from Pseudomonas cepacia as catalyst. Reactions were conducted in bulk, with molecular sieves, at 80°C, for 7 days to give poly(ricinoleic acid) with Mw > 1 x 10s (Scheme 4.3) [32]. This result is generally uncharacteristic of other reports on related monomers given that lipase-catalyzed esterification of secondary hydroxyls proceeds slowly (see below) and ricinoleic acid purity to achieve such molecular weights must be very high. 

Lipase-catalyzed synthesis of poly(l,4-butyl sebacate) from reactions of 1,4-butanediol and sebacic acid or activated derivatives of sebacic acid were studied by Linko et al. [51]. Reactions between 1,4-butanediol with sebacic acid,... 

The phase separation of reactants hindered attempts to carry out lipase-catalyzed synthesis of poly(butylene succinate) (PBS) from succinic acid and 1,4-butanediol via dehydration. Therefore, in order to obtain a monophasic reaction mixture, dimethyl succinate was used in place of succinic acid. [49] The reaction mixture remained monophasic during the reaction course, and after 21 h at 95 °C PBS with M of 38000 was obtained. 

Similarly, a telechelic polymer bearing carboxylic acid groups at both chain ends was formed by carrying out the lipase-catalyzed polymerization of DDL in the presence of divinyl sebacate [72]. In this case, divinyl sebacate functioned as a coupling agent creating poly(DDL) chains with hydroxyl groups at both termini. 

ROP of substituted 4-membered P-propiolactones, (P-PL), were reported using lipase-catalysis in bulk. oc-methyl-P-PL gave a polymer with an analogous structure to poly(lactic acid) (PLA). Pseudomonas fluorescent lipase-catalyzed ROP of a-methyl-P-PL in toluene was found to be selective for (S)- a-methyl-P-PL giving (S) enriched poly(oc-methyl-P-PL) with M ranging from 2000 to 2900 [101]. 

Multiarm heteroblock star-type copolymers of poly(lactic acid) (PLA) and poly(e-CL), poly(LA-co-e-CL) were prepared via a chemoenzymatic route [90]. Firstly, ROP of e-CL was initiated regioselectively from 6-OH site of ethyl glucopyrano-side (EGP) (see also above) using porcine pancreatic lipase as catalyst followed by termination of the EGP-PCL-OH terminus by lipase-catalyzed acetylated using vinyl acetate. Subsequently, Sn-catalyzed ROP of lactide was initiated from 2-, 3- and 4-OH groups of EGP to give a copolymer consisting of one poly(e-CL) arm with M = 1300 and three PLA arms so that the M of the final product was 11500 (Scheme 4.25). 

Scheme 4.27 Pseudomonas fluorescens lipase-catalyzed synthesis of poly (MBC-co-TMC).

In addition, the lipase-catalyzed copolymerization of PDL with a sugar carbonate (IPXTC) in toluene at 70 °C was studied [115], Novozym 435 was found to be the most effective lipase catalyst based on its ability to form PDL/IPXTC copolymers. For example, by this method, poly(PDL-co-19 mol % IPXTC) was prepared in 38% isolated yield in 5 days with M 4070. The copolymer formed consisted of PDL blocks with random interruptions by IPXTC units or short segments. 

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

J. (1995) Lipase-catalyzed synthesis of poly(1,4-butyl sebacate) from sebacic acid or its derivatives with 1,4-butanediol./. Biotechnol., 40 (2), 133-138. 

Jiang, Y., Liu, C., and Gross, R.A. (2008) Lipase-catalyzed synthesis of aliphatic poly(carbonate-co-esters). Macromolecules, 41 (13), 4671-4680. 

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. 

Cordova, A., Iversen, T., and Hult, K. (1999) Lipase-catalyzed formation of end-functionalized poly(e-caprolactone) by initiation and termination reactions. Polymer, 40 (24), 6709-6721. 

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. 

The enzymatic polymerization of optically pure d,d-, or L,L-lactide and meso D,L-lactide for the preparation of biocompatible and biodegradable poly(lactide) has received a lot of attention. Only the polymerization reactions of d,d-, and l,l-lactide will be discussed here as only these polymers are chiral in nature. Matsumura et al. reported the first lipase-catalyzed preparation of poly(L-lactide) (10) (Scheme 11.1) [18]. Polymerization reactions were performed in bulk at temperatures between 80 and 130 °C for 7 days using Pseudomonas cepacia lipase... 

Scheme 11.1 Lipase-catalyzed synthesis of poly(L-lactide) (10).

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