Lipase catalyst

The reaction systems used for modification of triglycerides usually consist of a lipase catalyst and a small amount of water dispersed in a bulk organic phase containing the reactants and, if required, a water immiscible solvent. The small amount of water in the reaction system partitions between the catalyst and the bulk organic phase. 

Calculated from Michaelis-Menten constants using lipase catalyst. Polymerization with zinc octanoate/butyl alcohol initiator system in bulk. 

Terminal-functionalized polymers such as macromonomers and telechelics are very important as prepolymer for construction of functional materials. Single-step functionalization of polymer terminal was achieved via lipase catalysis. Alcohols could initiate the ring-opening polymerizahon of lactones by lipase catalyst. The lipase CA-catalyzed polymerizahon of DDL in the presence of 2-hydroxyethyl methacrylate gave the methacryl-type polyester macromonomer, in which 2-hydroxyethyl methacrylate acted as initiator to introduce the methacryloyl group quanhtatively at the polymer terminal ( inihator method ).This methodology was expanded to the synthesis of oo-alkenyl- and alkynyl-type macromonomers by using 5-hexen-l-ol and 5-hexyn-l-ol as initiator, respechvely. 

Unactivated esters, typically alkyl esters, often show low reactivity toward lipase catalyst for transesterifications. In the case of the lipase-catalyzed polycondensation of dialkyl esters with glycols, the polymer of high molecular weight was not obtained. The molecular weight improved when vacuum conditions were used Mw reached more than 2 x 104 in the combination of diethyl sebacate and 1,4-butanediol catalyzed by lipase MM [30]. 

In lipase-catalyzed transesterifications, frequent use of enol esters as acyl agents has been seen [1, 5], since the leaving unsaturated alcohol irreversibly tautomerizes to an aldehyde or a ketone, leading to the desired product in high yields. The polymerization of divinyl adipate and 1,4-butanediol proceeded in the presence of lipase PF at 45 °C [39]. Under similar reaction conditions, adipic acid and diethyl adipate did not afford the polymeric materials, indicating the high polymerizability of bis(enol ester) toward lipase catalyst. 

Polymerization of oxiranes with succinic anhydride proceeded in the presence of PPL at 60 °C or 80 °C [63]. The ring-opening of the oxirane might proceed by a carboxylic acid catalyst, which is formed by the reaction of succinic anhydride with serine residue of the lipase catalyst. 

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)... 

In order to keep polyamides soluble in relatively apolar solvents, the use of flexible (macro)monomers such as a, co-(diaminopropyl)polydimethylsiloxane [52] or oligoethyleneglycol-based diamines [53, 54] has been proven to be a successful approach (Fig. 10). Poly condensations of dimethyl adipate with a variety of diamines were successful in bulk and at moderate temperatures between 60 and 100 °C (reaction A in Fig. 10). The low temperatures (60-100 °C) that suffice in these polymerizations also allow the use of monomers that are thermally instable, such as diethyl fumarate [53]. Moreover, multifunctional amines could be regioselectively polymerized up to molecular weights of 9 kDa, making lipase catalysts a valuable tool for the preparation of well-defined polyamides that can be further functionalized with active groups. 

Chapter 3 focuses on the increased understanding in enzymatic strategies for the production of well-defined polymers. A wide variety of (co)polymers has been synthesised and explored in a variety of applications using lipase catalysts. On the other hand, detailed studies also revealed the limitations of the use of lipases as a result of the monomer-activation mechanism, polymers of low polydispersity and quantitative degree of end-group functionality are difficult to attain. 

Valivety, R.H., Hailing, P.J. and Macrae, A.R. (1992) Reaction rate with suspended lipase catalyst shows similar dependence on water activity in different organic solvents. Biochim. Biophys. Acta, 1118, 218-222. 

Kulshrestha, A. S., Gao W., and Gross, R. A. 2005. Glycerol copolyesters Control of branching and molecular weight using lipase catalyst. Macromolecules, 38, 3193-3204. 

Alkali-catalyzed transesterifications have several drawbacks in addition to the problem of free fatty acids and water in the feedstock. They are energy intensive, recovery of the glycerol is difficult, the basic catalyst has to be removed from the product and the alkaline waste water requires treatment. These disadvantages could be circumvented by employing a lipase catalyst. But, in order to be economically viable, the enzyme costs have to be minimized through effective immobilization and recycling. 

Many dicarboxylic acids and their alkyl esters are commercially available however, they often showed low reactivity toward lipase catalyst. Thus, development of the reaction apparatus and reaction conditions has been made for efficient production of higher molecular weight polyesters. In the polycondensation of adipic acid and 1,4-butanediol, a horizontal two-chamber reactor was employed to remove the leaving water molecules with use of molecular sieves.192 A low-dispersity polyester with a degree of polymerization (DP) of 20 was obtained by the two-stage polymerization using Mucor mlehel lipase (lipase MM). 

Lipase catalysts have been used for functionalization of polymers. A terminal hydroxy group of poly-(e-CL) was reacted with carboxylic acids using lipase CA catalyst to give end-functionalized polyesters.231 Lipase MM catalyzed the regioselective transesterification of the terminal ester group of oligo (methyl methacrylate) with allyl alcohol.232 In the PPL-catalyzed reaction of racemic 2,2,2-trichloroethyl 3,4-epoxybutanoate with hydroxy-terminated PEG, the... 

Although there are notable exceptions as given below, the most common lipase-catalyst used for polyester synthesis is Candida antarctica lipase B (CALB) (please refer to Chapter 14 for more information on the structure and reaction mechanisms of CALB). The immobilized CALB catalyst that has been primarily used is Novozym 435, manufactured by Novozymes (Bagsvaerd, Denmark). Novozym 435 consists of CALB physically adsorbed within the macroporous resin Lewatit VPOC 1600 (poly[methyl methacrylate-co-butyl methacrylate], supplied by Bayer) (please refer to Chapter 3 for more information on Novozym 435). 

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. 

Uyama, H., Kikuchi, H., Takeya, K., and Kobayashi, S. (1995) Enzymatic ring-opening polymerization of lactones to polyesters by lipase catalyst unusually high reactivity of macrolides. Bull. Chem. Soc.Jpn.,... 

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

Again, the use of lipase catalyst for interesterification of edible fats and oils has advantages over the classical chemical catalysts. One of the most attractive features is the unique specificities possible with their use. Nonspecific lipases provide reactions like the random chemical catalyzed interesterification. Specific lipases make it possible to produce fats and oils with a customized triglyceride structure. The enzymatic process can be selective with the use of a positional specificity lipase. These processes are usually much slower and more sensitive to the reaction conditions to provide a better control over the reaction results. Also, the lipases can operate under milder reaction conditions, temperature and pressure, that minimize the formation of side products. 

---