Enzyme-catalyzed ring-opening

A very attractive and efficient method for the synthesis of L-aminoacids via DKR has been reported by Turner et al. [41a,b]. They employed enzyme-catalyzed ring opening of 5(4H)-oxazolones in combination with a catalytic amount of Et3N. The relatively low pKa of the C-4 proton (8.9) of oxazolones facilitates racemization. Hydrolysis of the ester obtained through DKR, followed by debenzoylation, yields L-aminoacids in excellent enantiomeric excess (99.5%) (Figure 4.16). In their initial studies, they employed Rhizomucor miehei lipase (Lipozyme) as the biocatalyst [41]. More recently, they have obtained excellent results employing CALB [41bj. This method has also been employed by Bevinakatti [41c,d] and Sih [41e,fj. 

Albertsson A-C, Srivastava RK (2008) Recent developments in enzyme-catalyzed ring-opening polymerization. Adv Drug Deliv Rev 60 1077-1093... 

Loeker EC, Duxbury CJ, Kumar R, Gao W, Gross RA, Howdle SM (2004) Enzyme-catalyzed ring-opening polymerization of e-caprolactone in supercritical carbon dioxide. Macromolecules 37 2450-2453... 

Feng Y, Kniifennann J, Klee D, Hdcker H (1999) Enzyme-catalyzed ring-opening polymerization of 3(S)-isopropylmorpholine-2,5-dione. Macromol Rapid Commun 20 88-90... 

An alternate approach, which also uses enzyme-catalyzed ring-opening of a lactone to generate a mechanism-activated inhibitor, was developed by Katzenellenbogen and his co-workers [183], who found enol lactones, exemplified by (13-8) and (13-9), to be potent, selective inhibitors of HLE. The haloenol lactone (13-9) was an irreversible inactivator of HLE and chymotrypsin, and after exposure to (13-9), active enzyme could not be regenerated even upon treatment with hydrazine. Enol lactone (13-8), on the other hand, was an alternate-substrate inhibitor, which produced only transient inhibition of HLE and chymotrypsin. These results have been interpreted to mean that, with the halo-substituted compounds, ring opening results in formation of an acyl-enzyme that contains a reactive halomethyl ketone, which then alkylates His-57. That these compounds... 

Okumara et al. [10] were the first to attempt the enzyme-catalyzed synthesis of oligoesters from a reaction between dicarboxylic acids and diols. Gutman et al. [11] reported the first study on polyester synthesis by enzyme-catalyzed polymerization of A-B type monomers. Two independent groups in 1993 [12, 13] were first to report enzyme-catalyzed ring-opening polymerization (ROP). Their studies focused on 7- and 6-membered unsubstituted cyclic esters, e-caprolactone (e-CL) and 8-valerolactone (8-VL), respectively. 

Matsumura, S., Beppu, H., Tsukuda, K., and Toshima, K. (1996) Enzyme-catalyzed ring-opening polymerization of (3-propiolactone. Biotechnol. Lett., 18 (9), 1041-1046. 

Srivastava, R.K. (2005) High-molecular-weight poly(l,5-dioxepan-2-one) via enzyme-catalyzed ring-opening polymerization. J. Polym. Sci. Part. A Polym. Chem., 43 (18), 4206-4216. 

Al-Azemi, T.F., Harmon, J.P., and Bisht, K.S. (2000) Enzyme-catalyzed ring-opening copolymerization of... 

Schwab, L.W., Kroon, R., Schouten, A.J., and Loos, K. (2008) Enzyme-catalyzed ring-opening polymerization of unsubstituted (3-lactam. Macromol. Rapid Commun., 29, 794-797. 

Figure 12.2 Enantioselective enzyme-catalyzed ring-opening polymerization of caprolactone from PHB-diol [10].

Albertsson, A.-C. Srivastava, R.K. High molecular weight aliphatic polyesters from enzyme-catalyzed ring-opening polymerization and their use ACS Polymer Preprints, 2006, 7(2), 245. 

FIGURE 3.38 Mechanism of enzyme-catalyzed ring-opening polymerization (ROP). 

FIGURE 3.39 Examples of cyclic monomers for enzyme-catalyzed ring-opening polymerization reactions. 

In order to further verify the involvement of catalytic amino acid residues in enzyme-catalyzed ring-opening polymerization, catalytic amino acids of the catalytic domain of the PHB depolymerase were replaced and evaluated for their polymerization activities. PHB depolymerases have structures that consist of a catalytic domain, a putative linker region, and a substrate binding domain (SBD). Three strictly conserved amino acids, serine, aspartate, and histidine, constitute the catalytic triad at the active center of the catalytic domain. The conserved serine is part of the so-called lipase-box... 

Enzyme-catalyzed ring-opening polymerization should open a new frontier for more types of polyesters, such as structural and elemental variations. Such examples may be the enzyme-catalyzed preparation of thio- and phospho-polyesters. 

Srivastava, R.K. and Albertsson, A.-C. (2007) Micro-block copolymers as a result of transesterfication catalyzing behavior of lipase-CA in sequential ROP. Macromolecules, 40(13), 4464-9. Srivastava, R.K. and Albertsson, A.-C. (2006) Porous scaffolds from high molecular weight polyesters synthesized via enzyme-catalyzed ring-opening polymerization. Biomacromolecules, 7(9), 2531-8. 

R. A., Kaplan, D.L. and Swift, G, (1997) Enzyme catalyzed ring-opening polymerization of (o-pentadecalactone. Macromolecules, 30, 2705-11,... 

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