Evaluation of enantioselectivity in lipase-catalyzed acylation of hydroxyalkylphosphine oxides

The lipase-catalyzed optical resolution of 2-, 3-, and 5-hydroxyalkyl phosphorus compounds 1 provided the corresponding optically pure diastereomers in good yields. (S_P, R)- and (R_P, S)-1 were acylated faster than (S_P, S)- and (R_P, R)-1. The stereoselectivity at the phosphorus atom changed with the flexibility of the active sites in the lipases. The stereoselectivity at the phosphorus atom was higher in the reaction of 1a than in the reaction of 1b,c. The reaction rate of ɛ-hydroxyalkylphosphine oxide 1c was faster than that of 1a, although less enantioselectivity was observed at the phosphorus atom.     

Application of lipase-catalyzed transformations for the synthesis of insect pheromones and related compounds

This review describes efficient means of preparing optically pure insect pheromones and related compounds via lipase-catalyzed enantioselective reaction on a large scale. (1) A new synthesis of the Japanese beetle pheromone, (R,Z)-(−)-5-(1-decenyl)oxacyclopentan-2-one, established by a combination of two lipase-catalyzed transformation was demonstrated. (2) A chemico-enzymatic procedure for the syntheses of both enantiomers of cupreous chafer beetle pheromone, (R,Z)- and (S,Z)-5-(1-octenyl)oxacyclopentan-2-one, was described. (3) An optical resolution of (±)-2,3-epoxy-8-methyl-1-nonanol, the key intermediate of the synthesis of gypsy moth pheromone, was demonstrated. (4) A practical chemico-enzymatic synthesis of (+)-disparlure in large scale was demonstrated. (5) A facile synthesis of carboxyalkyl acrylate, which is special monomers in the synthesis of the new polymers, by two lipase-catalyzed regioselective reactions was described.     

Enhanced performance of lipase-catalyzed kinetic resolution of secondary alcohols in monoether-functionalized ionic liquids

Several cationic monoether-functionalized ionic liquids (MEF-ILs) with different substituents were synthesized and used as media for kinetic resolution of secondary alcohols catalyzed by several lipases. The results indicate that Novozym 435 (an immobilized Candida antarctica Lipase B) had higher efficiency compared to other lipases in deracemization. The alkyl substituents at the 2- and 3-positions in the imidazolium ring of MEF-ILs were found to contribute to the increased enantioselectivity and enhancement of the reaction rate, respectively, while the higher stereo-hindrance of ether bonds decreased the activity. An enantioselectivity higher than 99% with 50% conversion of rac-1-phenylethanol was achieved using the catalyst system comprised of Novozym 435 and the MEF-IL 1-(3-ethoxypropyl)-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)imide. The catalytic system could be separated and reused without considerable activity loss. MEF-ILs can be a new class of enzyme-benign media suitable for lipase-catalyzed kinetic resolution of secondary alcohols.     

Kinetic resolution of propargylic alcohols via stereoselective acylation catalyzed by lipase PS-30

By using lipase PS-30 as catalyst, the kinetic resolution of a series of racemic propargylic alcohols has been achieved via stereoselective acylation. The value of kinetic enantiomeric ratio (E) reached up to 139. Substituent effect is briefly discussed.     

Synthesis of chiral building blocks for organic synthesis via lipase-catalyzed reaction: New method of enhancing enzymatic reaction enantioselectivity

The optically active building blocks for organic synthesis: tertiary carbinols, antitumor lignan, liquid crystals, 1,3-diene and biscyclopropyl compounds were synthesized through lipase-catalyzed reaction. This paper discusses ways in which organic chemists can expand the applicability of lipase-catalyzed reactions for use in designing a synthetic strategy. Several excellent examples are described in which lipase-catalyzed reactions were involved as the key steps. Because lipase-catalyzed reactions often offer insufficient enantioselectivity, a new method to enhance the enantioselectivity of a lipase-catalyzed reaction was demonstrated. Thiacrown ether technology was typically used to synthesize new optically active ,-difluoro-γ-lactone.     

Ester synthesis in lipase-catalyzed reactions

This review discusses the myriad of reaction systems employed in ester production catalyzed by lipases. Enzyme behavior in reaction systems is a consequence of certain structural patterns typical of lipases. Water has a profound effect on the lipase behavior either directly by affecting the hydration of the enzyme or indirectly by changing the nature of the reaction media and/or enzyme support materials. The significance of water is further emphasized with the understanding of its role in various reaction media and support materials. In addition to water, the media and support material are seldom inert and often interact with other factors affecting the reaction. Several methods of water removal and their effectiveness in lipase-catalyzed reactions are discussed. There is a recent surge of interest in modifying lipase systems with surfactants as studies demonstrate the potential of the enhanced performance of surfactant-modified lipases.     

Environmentally friendly, efficient resolution of racemic secondary alcohols by lipase-catalyzed enantioselective transesterification in ionic liquids in the presence of organic bases

The lipase-catalyzed enantioselective transesterification of racemic secondary alcohols was studied using vinyl acetate as acyl donor in two imidazolium-based ionic liquids vs. hexane (Scheme), both in the absence and presence of catalytic amounts of organic bases such as triethylamine (Et(3)N) or pyridine. The organic bases generally enhanced both the rate and enantioselectivity of the reaction. Further, the system 1-butyl-3-methyl-1H-imidazolium hexafluorophosphate/Candida antarctica lipase B ([bmim][PF(6)]/CALB) could be readily recycled four times without significant loss in activity or enantioselectivity.     

Molecular modeling of the enantioselectivity in lipase-catalyzed transesterification reactions.

Two strategies based on the use of subsets for calculating the enantioselectivity in lipase-catalyzed transesterifications using the CHARMM force field were investigated. Molecular dynamics was used in our search for low energy conformations. Molecular mechanics was used for refining these low energy conformations. A tetrahedral intermediate with a rigid central part was used for mimicking the transition state. The energy differences between the transition states of the diastereomeric enzyme-substrate complexes were calculated. The way of defining the subsets was based on two fundamentally different strategies. The first strategy used predefined parts of the enzyme and the substrate as subsets. The second approach formed energy-based subsets, varying in size with the substrates studied. The selection of residues to be included in these energy-based subsets was based on the energy of the interaction between the specific residue or water molecule and the transition state. The reaction studied was the kinetic resolution of secondary alcohols in transesterifications using the Candida antarctica lipase B as chiral biocatalyst. The secondary alcohols used in the study were 2-butanol, 3-methyl-2-butanol, and 3,3-dimethyl-2-butanol.     

Biocatalysis of nitro substituted styrene oxides by non-conventional yeasts

Yeast strains (410) from more than 45 different genera were screened for the enantioselective hydrolysis of nitro substituted styrene oxides. These strains included 262 yeasts with known epoxides hydrolase activity for various other epoxides. Epoxide hydrolase activity for p-nitrostyrene oxide (pNSO) (177 strains) and m-nitrostyrene oxide (mNSO) (148 strains) was widespread in the yeasts, while activity for o-nitrostyrene oxide (oNSO) was less ubiquitous (22 strains). The strains that displayed enantioselectivity in the hydrolysis of one or more of the nitro substituted styrene oxides (35 strains) were also screened against styrene oxide (SO). Rhodosporidium toruloides UOFS Y-0471 displayed the highest enantioselectivity for pNSO (ee 55%, yield 35%) while Rhodotorula glutinis UOFS Y-0653 displayed the highest enantioselectivity for mNSO (ee >98%, yield 29%), oNSO (ee 39%, yield 19%) and SO (ee >98%, yield 19%). (R)-Styrene oxide was preferentially hydrolysed to the corresponding (R)-diol with retention of configuration at the stereogenic centre. In the case of the nitro substituted styrene oxides the absolute configurations of the remaining epoxides and the formed diols were not established.     

Recent developments in lipase-catalyzed synthesis of polymeric materials

In the past three years, enzymatic polymerization has dramatically developed and provided many successful examples in the construction of functional polymeric materials. In this review, the lipase-catalyzed synthesis of polymeric materials is systematically summarized, focusing on the synthesis of complex and well-defined polyesters. Exploration of novel biocatalysts and reaction media is described, with particular emphasis on the enzymes obtained via immobilization or protein engineering strategies, green solvents and reactors. Enzymatic polyester synthesis is then discussed with regard to the different reaction types, including ring-opening polymerization, polycondensation, combination of ring-opening polymerization with polycondensation, and chemoenzymatic polymerization. Using enzymatic polymerization, many polymeric materials with tailor-made structures and properties have been successfully designed and synthesized. Finally, recent developments in catalytic kinetics and mechanistic studies through the use of spectroscopy, mathematics and computer techniques are introduced. Overall, the review demonstrates that lipase-catalyzed synthesis of polymeric materials could be a promising platform for green polymer chemistry, and will be potential to produce biodegradable and biocompatible polymers.     

Altering lipase activity and enantioselectivity in organic media using organo-soluble bases: Implication for rate-limiting proton transfer in acylation step

With the hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl esters via a partially purified papaya lipase (PCPL) in water-saturated isooctane as the model system, the enzyme activity, and enantioselectivty is altered by adding a variety of organo-soluble bases that act as either enzyme activators (i.e., TEA, MP, TOA, DPA, PY, and DMA) or enzyme inhibitors (i.e., PDP, DMAP, and PP). Triethylamine (TEA) is selected as the best enzyme activator as 2.24-fold increase of the initial rate for the (S)-ester is obtained when adding 120 mM of the base. By using an expanded Michaelis-Menten mechanism for the acylation step, the kinetic analysis indicates that the proton transfer for the breakdown of tetrahedral intermediates to acyl-enzyme intermediates is the rate-limiting step, or more sensitive than that for the formation of tetrahedral intermediates when the enzyme activators of different pKa are added. However, no correlation for the proton transfers in the acylation step is found when adding the bases acting as enzyme deactivators.     

Adverse effect of chloride impurities on lipase-catalyzed transesterifications in ionic liquids

The adverse influence of chloride impurities on the lipase-catalyzed transesterification in ionic liquid is described. The activity of lipase from Rhizomucor miehei exponentially decreased with increasing Cl⁻ content in 1-octyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl] amide, [Omim][Tf₂N], and the activity of lipase in [Omim][Tf₂N] mixture containing 2% [Omim] [Cl] was only about 2% of the activity in pure [Omim][Tf₂N]. The activity of lipase from Candidantarctica linearly decreased at about 5% with every 1% increase in [Omim][Cl] with there being no activity in [Omim][Tf₂N] containing about 20% [Omim][Cl].     

Improvement of the enantioselectivity of lipase-catalyzed naproxen ester hydrolysis in organic solvent

A method is presented to improve the enantioselectivity of lipase-catalyzed hydrolysis of naproxen methyl ester in water-saturated isooctane. It is shown that coupling of the enantioselective hydrolysis of Naproxen methyl ester with the photo-dissociation methanol leads to the photocatalytic conversion of methanol into water, by which the equilibrium constant (K) of the lipase-catalyzed hydrolysis was changed. The equilibrium yield and enantiomeric excess are increased. Because the lipase would not dissolve in the organic solvent, it was adsorbed on photocatalyst particles, which may facilitate the isolation of enzyme from reaction system.     

Resolution of 2-nitroalcohols by Burkholderia cepacia lipase-catalyzed enantioselective acylation

Racemic 2-nitro-1-phenylethanol was resolved by via enantioselective transesterification catalyzed by Burkholderia cepacia lipase. The reaction afforded excellent E values (E > 200) and enantioselectivity (up to >99% enantiomeric excesses [ee]) of both remaining substrates and acetylated product. Moreover, the lipase displayed high enantioselectivity in the resolution of additional 2-nitroalcohols (E up to >200). This method provides an efficient alternative for obtaining enantiopure 2-nitroalcohols.     

Resolution of secondary alcohols via Carica papaya lipase-catalyzed enantioselective acylation

The Carica papaya lipase-catalyzed acylation of benzylcarbinols with vinyl hexanoate proceeded smoothly and enantiospecifically (E > 200), affording the R-esters and leaving the S-alcohols intact. Thus, this plant lipase proved to be a promising biocatalyst for the resolution of alcohols as well as for that of carboxylic acids reported earlier.     

Lipase-catalyzed optical resolution of trifluoro(aryl)ethanols

Optical resolutions of racemic 2,2,2-trifluoro-1-(aryl)ethanols — (1-naphthyl), (2-naphthyl), (4-methylnaphthyl), (phenyl), (1-pyrenyl) — were achieved by lipase-catalyzed enantioselective acetylations with vinyl acetate as an acetyl donor in octane, and (S)-acetates and (R)-alcohols were obtained. Among the lipases tested, lipase from Pseudomonas aeruginosa (lipase LIP, Toyobo) showed good enantioselectivity for above ethanols. However, no acetylation occurred with sterically hindered alcohols — (9-phenanthryl), (9-anthryl), (2-methylnaphthyl), (2, 4, 6-trimethylphenyl) — by various lipases. The resolutions of the three alcohols were carried out by the enantioselective alcoholysis or hydrolysis of their chloroacetates by lipase LIP.     

Design of phosphonium ionic liquids for lipase-catalyzed transesterification

Ionic liquids are now recognized as solvents for use in lipase-catalyzed reactions; however, there still remains a serious drawback in that the rate of reaction in an ionic liquid is slower than that in a conventional organic solvent. To overcome this problem, attempts have been made to evolve phosphonium ionic liquids appropriate for lipase-catalyzed reaction; several types of phosphonium salts have been prepared and their capability evaluated for use as solvent for the lipase-catalyzed reaction. Very rapid lipase PS-catalyzed transesterification of secondary alcohols was obtained when 2-methoxyethyl(tri-n-butyl)phosphonium bis(trifluoromethanesulfonyl)imide ([MEBu₃P][NTf₂]) was used as solvent, affording the first example of a reaction rate superior to that in diisopropyl ether.     

Optimized lipase-catalyzed synthesis of adipate ester in a solvent-free system

Immobilized Candida antarctica lipase-catalyzed esterification of adipic acid and oleyl alcohol was investigated in a solvent-free system (SFS). Optimum conditions for adipate ester synthesis in a stirred-tank reactor were determined by the response surface methodology (RSM) approach with respect to important reaction parameters including time, temperature, agitation speed, and amount of enzyme. A high conversion yield was achieved using low enzyme amounts of 2.5% w/w at 60°C, reaction time of 438 min, and agitation speed of 500 rpm. The good correlation between predicted value (96.0%) and actual value (95.5%) implies that the model derived from RSM allows better understanding of the effect of important reaction parameters on the lipase-catalyzed synthesis of adipate ester in an organic solvent-free system. Higher volumetric productivity compared to a solvent-based system was also offered by SFS. The results demonstrate that the solvent-free system is efficient for enzymatic synthesis of adipate ester.