Enzymatic ring-opening synthesis

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). 

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... 

Well-defined sophorolipid biosurfactant analogs were also prepared via enzymatic synthesis for the evaluation of the bioactivity and as building blocks for the preparation of glycolipid-based polymers [107]. The direct enzymatic ring-opening polymerization of lactone sophorolipids (SLs) was carried out with lipases. The reaction proceeded with the formation of mono-acylated lactone SLs and the subsequent conversion of the intermediates to oligomers and polymers (Scheme 12) [108]. 

Uyama H, Takeya K, Kobayashi S (1993) Synthesis of polyesters by enzymatic ring-opening copolymerization using lipase catalyst. Proc Jpn Acad B 69 203—207... 

Sha K, Li D, Li Y, Liu X, Wang S, Guan J. Synthesis, characterization, and micellization of an epoxy-based amphiphilic diblock copolymer of e-caprolactone and glycidyl methacrylate by enzymatic ring-opening polymerization and atom transfer radical polymerization. J Polym Sci, Part A Polym Chem 2007 45 5037-49. 

In polyester synthesis via ring-opening polymerizations, metal catalysts are often used. For medical applications of polyesters, however, there has been concern about harmful effects of the metallic residues. Enzymatic synthesis of a metal-free polyester was demonstrated by the polymerization of l,4-dioxan-2-one using Candida antarctica lipase (lipase CA). Under appropriate reaction conditions, the high molecular weight polymer (molecular weight = 4.1 x 10" ) was obtained. 

Matsumura S. Enzymatic Synthesis of Polyesters via Ring-Opening Polymerization. Vol. 194, pp. 95-132. 

Synthesis of aminopolysaccharides, therefore, is one of the important research areas in the field of functional materials, examples of biorelated polymers, antibacterial substance, and biodegradable polymers as well as materials for drugs and matrices of drug delivery systems. Only a few methods, however, such as ring-opening polymerization and enzymatic polymerization have been available for the precision synthesis of aminopolysaccharides [4,5],... 

The polymerization of 1 mentioned above should be compared with the enzymatic synthesis of chitin reported by Kobayashi and coworkers, in which an oxazoline derivative of A, A -diacetylchitobiose, the repeating unit of chitin was polymerized in the presence of chitinase enzyme via ring-opening addition process to give an artihcial chitin (Scheme 6) [5]. The method using an enzyme, however, may not enable synthesis of nonnatural-type aminopolysaccharide because the reaction catalyzed by chitinase enzyme is limited to the formation of (1 4)-P-glycosidic linkage. 

Over the years we have developed methods for the direct synthesis of hydrolytically and/or enzymatically degradable microspheres by ring-opening polymerization of e-caprolactone and lactides [6-12]. The diameters of these microspheres are usually less than 3 xm. In this chapter we discuss... 

Knani D, Gutman AL, Kohn DH (1993) Enzymatic polyesterification in organic media. Enzyme-catalyzed synthesis of linear polyesters. I. Condensation polymerization of linear hydroxyester. II. Ring-opening polymerization of e-caprolactone. J Polym Sci A Polym Chem 31 1221-1232... 

Kato, M., Toshima, K., and Matsumura, M. (2007) Enzymatic synthesis of polythioester by the ring-opening polymerization of cyclic thioester. Biomacromolecules, 8 (11), 3590-3596. 

The most extensively studied enzymatic polymerization system is that of polyesters via polycondensations or ring-opening polymerizations. The state of the art of in vitro enzymatic polyester synthesis is reviewed in Chapter 4. 

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