Lipase-catalyzed transesterification

Combination of lipase-catalyzed transesterification with unsaturated vinyl esters as acyl donors and ring-closing metatheses (RCMs) have also been reported [146-148]. Two groups applied this strategy for the synthesis of goniothalamin from cinnamaldehyde [147,148]. The key steps were a transesterification using vinyl acrylate as acyl donor, followed by an RCM, as depicted in Figure 6.55. 

Homochiral (5)- and (f )-l-(2-furyl)ethanols were prepared from 21 by lipase-catalyzed transesterification with vinyl acetate. The pure enantiomers are preciusors for the syntheas of L-and D-daunomycin <96TA907>. 

One of the most important characteristics of IL is its wide temperature range for the liquid phase with no vapor pressure, so next we tested the lipase-catalyzed reaction under reduced pressure. It is known that usual methyl esters are not suitable for lipase-catalyzed transesterification as acyl donors because reverse reaction with produced methanol takes place. However, we can avoid such difficulty when the reaction is carried out under reduced pressure even if methyl esters are used as the acyl donor, because the produced methanol is removed immediately from the reaction mixture and thus the reaction equilibrium goes through to produce the desired product. To realize this idea, proper choice of the acyl donor ester was very important. The desired reaction was accomplished using methyl phenylth-ioacetate as acyl donor. Various methyl esters can also be used as acyl donor for these reactions methyl nonanoate was also recommended and efficient optical resolution was accomplished. Using our system, we demonstrated the completely recyclable use of lipase. The transesterification took place smoothly under reduced pressure at 10 Torr at 40°C when 0.5 equivalent of methyl phenylthioacetate was used as acyl donor, and we were able to obtain this compound in optically pure form. Five repetitions of this process showed no drop in the reaction rate (Fig. 4). Recently Kato reported nice additional examples of lipase-catalyzed reaction based on the same idea that CAL-B-catalyzed esterification or amidation of carboxylic acid was accomplished under reduced pressure conditions. ... 

Alkyl esters often show low reactivity for lipase-catalyzed transesterifications with alcohols. Therefore, it is difficult to obtain high molecular weight polyesters by lipase-catalyzed polycondensation of dialkyl esters with glycols. The molecular weight greatly improved by polymerization under vacuum to remove the formed alcohols, leading to a shift of equilibrium toward the product polymer the polyester with molecular weight of 2 x 10" was obtained by the lipase MM-catalyzed polymerization of sebacic acid and 1,4-butanediol in diphenyl ether or veratrole under reduced pressure. ... 

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. 

Miyazawa, T., Kurita, S., Ueji, S., Yamada, T. and Shigeru, K., Resolution of mandelic acids by lipase-catalyzed transesterifications in organic media inversion of enantioselectivity mediated by the acyl donor. J. Chem. Soc. Perkin Trans. 1, 1992, 18, 2253-2255. 

Lipase-catalyzed transesterification of (3-nitroalcohol substrates had not previously been reported and required careful optimization of the reaction conditions. A series of enzymes were screened, followed by acyl donors. From these results, the lipase Pseudomonas cepacia (PS-C I) (for more... 

The enzymatic resolution of racemic substrates now is a well-established approach for the synthesis of single enantiomers [1, 2]. A representative example is the kinetic resoluhon of secondary alcohols via lipase-catalyzed transesterification for the preparation of enantiomericaUy enriched alcohols and esters [3], The enzymatic resolution in general is straightforward and satisfactory in terms of optical purity, but it has an intrinsic Hmitation in that the theoretical maximum yield of a desirable enantiomer cannot exceed 50%. Accordingly, additional processes such as isolation, racemization and recycling of unwanted isomers are required to obtain the desirable isomer in a higher yield (Scheme 1.1). 

Fig. 4. a rac-Phenylethylamine (PEA) and 2-methoxy-J T-[(li )-l-phenylethyl]-acetamide (MET) are substrate and product in a lipase catalyzed transesterification, b Linear relationship between relative signal intensities in MALDI-MS and the relative concentrations of PEA/d5-labeled PEA. c Comparison of decrease in PEA during enzymatic conversion as measured by quantitative MALDI-MS and gas chromatography (GC)... 

The situation is summarized from a slightly different perspective in Figure 2.2. Here, data obtained using the same set of organic solvents have been plotted. The porcine pancreatic lipase-catalyzed transesterification of sulcatol (6-methyl-5-hepten-2-ol) with butyric acid trifluoroethyl ester [81] has been chosen (arbitrarily) to calibrate the solvents. It is clear that, irrespective of the solvent descriptors that one may aim to investigate, different systems are seen to respond differently to the same (change of) medium. 

Lipase-catalyzed transesterification to prepare polyesters (replacing the traditional chemical polymerization at >200 °C) has received considerable attention in recent years. CaLB was found to mediate polyester synthesis in the ionic liquids [BMIm][BF4], [BMIm][PF6], and [BMIm][ Tf2N] at 60°C [110, 111, 112], but the molecular weight of the product was rather low compared with that in a solventless system [113], perhaps owing to the high viscosity of ionic liquid media. 

Enzymatic reactions now have a sound place in contemporary synthetic methodology. Illustrative of this, lipase-catalyzed transesterification of the racemic alcohol 65 has been used effectively to produce (6)-(+)-66 (LipaseQL, 0-5 °C, 4 h 47% yield >99% ee), plus the (R)-(—)-acetoxy derivative 67 (Equation 8). The 1-benzazepine derivative 66 was then converted to a chiral precursor required for the synthesis of the nonpeptide vasopressin V2 receptor agonist, OPC-51803 <2002H(58)635>. The synthesis of a 1-benzazepine-based antagonist (OPC-41061) at this receptor has also been reported <2002H(56)123>. 

R. Bovara, G. Carrea, G. Ottolina, and S. Riva, Effects of water activity on Vm3X and Km of lipase catalyzed transesterification in organic media, Biotechnol. Lett. 

Chulalaksananukul, W. Condoret, J. S. Combes, D. Geranyl Acetate Synthesis by Lipase-Catalyzed Transesterification in Supercritical Carbon Dioxide. Enzyme Microb. Technol. 1993, 15, 691-698. 

The improvement of the enantioselectivity E in kinetic resolution of a primary alcohol (10) through lipase-catalyzed transesterification was studied using a chiral acyl donor 11. The combination of the lipase, solvent and acyl donor was effective for the enantioselectivity.62... 

Numerous examples can be found in literature and only a few selected examples are included in this survey. Schurig et al reported a series of reports about the utility of isopropenyl acetate as an innocuous acyl donor in the lipase-catalyzed transesterification of secondary alcohols. The non-reacting alcohol enantiomers were obtained in > 99%... 

Figure 14 Lipase-catalyzed transesterification of secondary alcohols using isopropenyl acetate as acyl donor in...

Figure 15 Gas chromatographic chiral separation of (left) racemic l-(4-methoxy-phenyl)ethanol 22 and its corresponding acetate 22a (reference) and (right) lipase-catalyzed transesterification of l-(4-methoxy-phenyl)ethanol 22 (4 hrs) using isopropenyl acetate as acyl donor in toluene as organic solvent ees= 99.9 eep= 87 conv. =53.4, E=141.

The kinetic resolution of racemic l-(benzofuran-2-yl)ethanol rac-33 having different substituents on the benzene was reported ring using lipase-catalyzed transesterification with vinyl acetate as acyl donor. The reaction afforded (lA)-l-acetoxy-l-(benzofuran-2-yl)ethanes (A)-34 and (16)-l-benzofuran-2-yl)ethanols (S)-33 in highly enantiopure form.65... 

Diols of different structures such as the meso-diol 76 (Fig. 41), the C2-symmetric diol rac-79 (Fig. 42), the diol rac-82 in which the primary hydroxy group is protected (Fig. 43) and the unprotected diol rac-84 with a primary and secondary hydroxy group (Fig. 44) were used as substrates in the lipase-catalyzed transesterification using vinyl acetate as acyl donor in organic solvents with the aim to prepare chiral buildings blocks of high enantiomeric purity.86... 

An efficient synthesis of (R)- and (S)-1 -amino-2,2-difluorocycloropanecarboxylic acid (DFACC) 91 via lipase-catalyzed desymmetrization of prochiral diols 89 and prochiral diacetates 92 was recently reported.28 Thus, the lipase-catalyzed transesterification of 89 using vinyl acetate as acyl donor in benzene di-z-propyl ether (20 1) as organic solvent... 

Ghanem, A. Schurig, V. Per-acetylated /J-Cyclodextrin as additive in enzymatic reactions enhanced reaction rate and enantiomeric ratio in lipase-catalyzed transesterifications in organic solvents. Tetrahedron Asymmetry 2001, vol 12/19. pp 2761-2766. 

Ghanem, A. The Utility of cyclodextrins in lipase-catalyzed transesterification in organic solvents enhanced reaction rate and enantioselectivity. Org. Biomol. Chem., 2003, 1, 1282 -1291. 

Ghanem, A. Schurig, V. Lipase-catalyzed transesterification of secondary alcohols using isopropenyl acetate as acyl donor in organic solvents. Monateshefte fur chemie, 2003, 134, 1151-1157. 

Kawasaki, M. Goto, M. Kawabata, S. Kometani, T. The effect of vinyl esters on the enantioselectivity of the lipase-catalyzed transesterification of alcohols. Tetrahedron Asymmetry 2001, 12, 585-596. 

Wielechowska, M. Plenkiewicz, J. -Alkylthio-3-aryloxypropan-2-ols synthesis and enantiomer separation by lipase-catalyzed transesterification. Tetrahedron Asymmetry 2003, 14, 3203-3210. 

Theil, F. Enantioselective lipase-catalyzed transesterifications in organic solvents. Methods in Biotechnology, 2001, 15, 277-289. 

The selective enzyme-catalyzed acylation of carbohydrates is of great interest, as of carbohydrates fatty acid esters of carbohydrates have important applications in detergents, cosmetics, foodstuff, and pharmaceuticals because of their surface-active properties. Monoacylated sugars have been synthesized by lipase-catalyzed transesterifications of activated esters in pyridine and by protease-catalyzed esterifications in DMF. A most remarkable new development... 

While diketene remains a very important synthetic precursor, there has been increasing interest in the chemistry of a-methylene-/3-lactones, 3-methylene-2-oxetanones. However, unlike diketene, which can be readily synthesized by the dimerization of aldehydic ketenes, there are few methods for the synthesis of a-methylene-/3-lactones in the literature. Recent strategies for the preparation of the compounds are discussed in Section 2.05.9.2. The kinetic resolution of racemates of alkyl-substituted a-methylene-/3-lactones has been carried out via a lipase-catalyzed transesterification reaction with benzyl alcohol (Equation 21) <1997TA833>. The most efficient lipase tested for this reaction was CAL-B (from Candida antarctica), which selectively transesterifies the (A)-lactone. At 51% conversion, the (R)-f3-lactone, (R)-74, and (A)-/3-hydroxy ester, (S)-75, were formed in very high enantio-selectivities (up to 99% ee). 

Du, W., Xu, Y., and Liu, D. 2003. Lipase-catalyzed transesterification of soya bean oil for biodiesel production during continuous batch operation. Biotechnol. Appl. Biochem.,38,103-106. 

Li, L., Du, W., Liu, D., Wang, L., and Li, Z. 2006. Lipase-catalyzed transesterification of rapeseed oils for biodiesel production with a novel organic solvent as the reaction medium. /. Mol. Catal. B Enzym., 43, 58-62. 

In the food industry, lipases are used in lipid modification processes. In these processes the texture, digestibility, or physical properties of natural lipids are modified by lipase-catalyzed transesterification reactions with lipids other than the original fatty acids. In the baking industry, lipases are used to influence the quality of bread through modification of the wheat flour lipids. Finally lipases are used for flavor enhancement of cheese in the dairy industry. 

Subsequently the groups of Williams [7] and Backvall [8] showed, in 1996 and 1997, respectively, that lipase-catalyzed transesterification of alcohols could be combined with transition metal-catalyzed racemization to produce an efficient dynamic kinetic resolution of chiral secondary alcohols (Fig. 9.2). 

H. H., Scheper, T Kolisis, F.N. (1993), Factors affecting the lipase catalyzed transesterification reactions of 3-hydroxy esters in organic solvents, Tetrahedron Asymmetry 4, 1007 -1016. 

The resulting dynamic nitroaldol system was subsequently challenged with lipase-catalyzed transesterification reactions using different lipases and operational... 

To investigate the lipase enantiomeric specificity, HPLC was used to monitor the enantiomeric ratios of products 22C and 22A. From these analyses, 99% and 98% ee of ester products 22C and 22A, respectively, were obtained and shown to have -configuration. This revealed that lipase-catalyzed transesterification is an efficient resolution technique since only two products were selected from 20 p-nitroalcohol substrates. 

---