Enzymatic ring-opening

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. 

Uyama H, Kobayashi S (1996) Enzymatic ring-opening polymerization of macrolides to polyesters. In Yalpani M (ed) Biomedical functions and biotechnology of natural and artificial polymers. ATL Press, Schrewsbury, p 5... 

The parent drug phensuximide (4.188) was not enzymatically cleaved, suggesting that Af-alkylation abolishes enzymatic ring opening. Furthermore, no ring-opened metabolites of methsuximide (4.189) were detected. In this case, however, disubstitution of C(2) rather than Afalkylation prevented hydrolysis, since 2-methyl-2-phenylsuccinimide (4.190), its TV-demethylated metabolite, was not a substrate of DHPase [119]. 

Pahnans et al. prepared 5 by the reaction of [RuCl2(p-cymene)]2 and 2-phenyl-2-aminopropionamide in the presence of potassium carbonate. They used 5 in an iterative tandem catalysis for the synthesis of chiral oligoesters. The enzymatic ring opening of 6-methyl-e-caprolactone was combined with ruthenium-catalyzed alcohol racemization to produce optically active oligomers of 6-methyl-e-capro-lactone [23] (Scheme 1.17). 

Extension of DKR to polymer chemistry would readily result in chiral polyesters, polycarbonates, or polyamides from an optically inactive monomer mixture. Scheme 10 describes three variants of chemoenzymatic catalysis applied in polymer chemistry that recently appeared in the literature. Route A uses AA and BB monomers to prepare chiral polymers from racemic/diasteromeric diols. Route B converts an enantiomer mixture of AB monomers to homochiral polymers. Route C is the enzymatic ring-opening polymerization of co-methylated lactones to homochiral polyesters. Details will be given in Sect. 3.4.2. 

Figure 6.2 Enzymatic ring-opening polymerization of e-caprolactone initiated by 2-mercaptoethanol.

As for the enzymatic ring-opening polymerization of e-CL, various commercially available lipases have been tested as a catalyst. Several crude lipases (PPL, lipases CR, PC, and Pseudomonas fluorescens lipase (lipase PF)) induced the polymerization however, a... 

Uyama, H., and Kobayashi, S. (1993) Enzymatic ring-opening polymerization of lactones catalyzed by lipase. Chem. Lett., 22 (7), 1149-1150. 

Enzymatic ring-opening polymerization and copolymerization of 8-octanolide by lipase catalyst. Macromolecules, 31 (17), 5655-5659. 

Wu, R., Al-Azemi, T.F., and Bisht, K.S. (2008) Functionalized polycarbonate derived from tartaric acid enzymatic ring-opening polymerization of a seven-membered cyclic carbonate. Biomacromolecules, 9 (10), 2921-2928. 

Preparation of poly(P-malic acid) by enzymatic ring-opening... 

Soeda, Y., Okamoto, T., Toshima, K., and Matsumura, S. (2002) Enzymatic ring-opening polymerization of oxiranes and dicarboxylic anhydrides. Macromol. Biosci., 2 (9), 429-436. 

Chiral, hydroxy functional polycarbonates were prepared by the enzymatic ring opening polymerization (ROP) of a seven-membered cyclic carbonate (12) derived from L-tartaric acid (Scheme 11.3) [24]. Among others Novozym 435, PFL, and... 

Route a uses AA and BB monomers to enzymatic ring opening polymerization of... 

Nakaoki, T., Kitoh, M., and Gross, R.A. (2005) Enzymatic ring opening polymerization of Ip-caprolactone in supercritical C02. ACS Symp. Ser., 900, (Polymer Biocatalysis and Biomaterials), 393-404. 

Villarroya, S., Zhou, J., Heise, A., and Howdle, S.M. (2006) Simultaneous enzymatic ring opening polymerization and RAFT-mediated polymerization in supercritical C02. Chem. Commun. (Camb.), 42, 4383-4385. 

Baum, I., Schwab, L., Loos, K., and Fels, G. (2010), Mechanistic insight into the enzymatic ring-opening polymerization of unsubstituted P-lactam catalyzed by Candida antarctica lipase B, submitted for publication. 

Figure 16.6 Enzymatic ring opening of cyclodextrin and the hydrolysis of linear oligosaccharides to glucose.

Chapter 14 introduces an interesting way to establish/solve the mechanism of enzymatic polymerizations via computer simulation. This method is quite well-established in other fields of chemistry but has only been used for solving the reaction mechanism of one enzymatic polymerization (the enzymatic ring opening polymerization of (i-lactam). The outline of the technique in this chapter proves the power of this method and hopefully inspires future research on other enzymatic polymerization mechanisms. 

The final enzyme discussed in the chapter, haloalcohol dehalogenase, catalyzes the formation of epoxides from halohydrins. However, the reverse reaction, the ring opening of epoxides with nonhalide nucleophiles such as cyanide, azide, and nitrite, has been exploited commercially to generate /3-substituted alcohols that are potential synthons. For this reason, the regioselectivity of the enzymatic ring opening reaction is of... 

Heise, Palmans, de Geus, Villarroya and their collaborators (17,41,42) have been working on a chemoenzymatic cascade synthesis to prepare block copolymers. They combine enzymatic ring-opening polymerization (eROP) and atom transfer radical polymerization (ATRP). The synthesis of block copolymers was successful in two consecutive steps, i.e., eROP followed by ATRP. In the one-pot approach, block copolymers could be obtained by sequential addition of the ATRP catalyst, but side reactions were observed when all components were present from at the onset of reactions. A successful one-pot synthesis was achieved by conducting the reaction in supercritical carbon dioxide. 

In recent years, the enzymatic synthesis of biodegradable polyesters was focused on the polycondensation method (22,23). Among the very few successful example of enzymatic ring-opening polymerization for polyesters synthesis, Novozyme-435 (immobilized lipase B from Candida antartica) has been proved an effective catalyst for polycaprolactone (PCL) synthesis in toluene (24). Considering the low cost and high recyclablity of IPPL, we also... 

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