Immobilization does not influence the enantioselectivity of CAL-B catalyzed kinetic resolution of secondary alcohols

Decreasing enantioselectivity (E-value) by increasing conversion has been observed in transesterification reactions of secondary alcohols catalyzed by a pure protein formulation of lipase B from Candida antarctica (Novozym 525 F). Addition of a range of enantiopure alcohols caused a temporary increase in selectivity of the transesterification reaction of 3-chloro-1-phenoxy-2-propanol with vinyl butanoate. The corresponding immobilized lipase B, (Novozym 435) showed a similar relationship between the E-value and degree of conversion.     

Chemoenzymatic Synthesis of 2-Arachidonoylglycerol, An Endogenous Ligand for Cannabinoid Receptors

A simple and efficient synthesis of 2-arachidonoyl glycerol, an endogenous agonist for cannabinoid receptors was achieved using Novozym 435, immobilized lipase from Candida antarctica.     

Enhanced selectivity in Novozym 435 catalyzed kinetic resolution of secondary alcohols and butanoates caused by the (R)-alcohols

In esterifications of secondary alcohols catalyzed by immobilized lipase B from Candida antarctica (Novozym 435) the E-values decreased during the reaction. Hydrolysis of the corresponding butanoates showed the opposite effect. When an enantiopure (R)-alcohol, related but different, was added to the transesterification reaction, the E-value was significantly enhanced.     

Polyesters from Macrolactones Using Commercial Lipase NS 88011 and Novozym 435 as Biocatalysts

The demand for environmentally friendly products allied with the depletion of natural resources has increased the search for sustainable materials in chemical and pharmaceutical industries. Polyesters are among the most widely used biodegradable polymers in biomedical applications. In this work, aliphatic polyesters (from globalide and ω-pentadecalactone) were synthesized using a new commercial biocatalyst, the low-cost immobilized NS 88011 lipase (lipase B from Candida antarctica immobilized on a hydrophobic support). Results were compared with those obtained under the same conditions using a traditional, but more expensive, commercial biocatalyst, Novozym 435 (lipase B from C. antarctica immobilized on Lewatit VP OC). When NS 88011 was used in the polymerization of globalide, longer reaction times (240 min)—when compared to Novozym 435—were required to obtain high yields (80–90 wt%). However, higher molecular weights were achieved. When poly(ω-pentadecalactone) was synthesized, high yields and molecular weights (130,000 g mol^?1) were obtained and the enzyme concentration showed strong influence on the polyester properties. This is the first report describing NS 88011 in polymer synthesis. The use of this cheaper enzymatic preparation can provide an alternative for polyester synthesis via enzymatic ring-opening polymerization.     

Syntheses of Enantiopure Aliphatic Secondary Alcohols and Acetates by Bioresolution with Lipase B from <em>Candida antarctica</em>

The lipase B from Candida antarctica (Novozym 435^?, CALB) efficiently catalyzed the kinetic resolution of some aliphatic secondary alcohols: (±)-4-methylpentan-2-ol (1), (±)-5-methylhexan-2-ol (3), (±)-octan-2-ol (4), (±)-heptan-3-ol (5) and (±)-oct-1-en-3-ol (6). The lipase showed excellent enantioselectivities in the transesterifications of racemic aliphatic secondary alcohols producing the enantiopure alcohols (>99% ee) and acetates (>99% ee) with good yields. Kinetic resolution of rac-alcohols was successfully achieved with CALB lipase using simple conditions, vinyl acetate as acylating agent, and hexane as non-polar solvent.     

Lipase-mediated selective acetylation of primary alcohols in ethyl acetate

An environmental friendly process to selectively acetylate primary alcohols was demonstrated. The esterification process consists of treatment of a primary alcohol in the presence of immobilized C. antarctica lipase (Novozyme-435) in ethyl acetate at room temperature. Primary alcohols were acetylated in the presence of secondary alcohols and phenols.     

CO2-expanded bio-based liquids as novel solvents for enantioselective biocatalysis

For the first time, CO₂-expanded bio-based liquids were reported as novel and sustainable solvents for biocatalysis. Herein, it was found that by expansion with CO₂, 2-methyltetrahydrofuran (MeTHF), and other bio-based liquids, which were not favorable solvents for immobilized Candida antarctica lipase B (Novozym 435) catalyzed transesterification, were tuned into excellent reaction media. Especially, for the kinetic resolution of challenging bulky secondary substrates such as rac-1-adamantylethanol, the lipase displayed very high activity with excellent enantioselectivity (E value > 200) in CO₂-expanded MeTHF (MeTHF concentration 10% v/v, 6 MPa), whereas there was almost no activity observed in conventional organic solvents.     

Highly enantioselective enzymatic resolution of cis-fused octalols mediated by Candida antarctica lipase (Novozym 435)

Optically active cis-fused octalin acetates have been prepared by esterification of cis-fused octalols using Candida antarctica lipase (CALB—Novozym 435). The enzyme efficiently resolved the racemic octalols by kinetic resolution, to afford cis-fused octalols and cis-fused octalin acetates with high enantiomeric excesses (up to >99%) and good yields (>40%).     

Enantiomerically pure organoseleno-1-arylethanols by enzymatic resolution with Candida antarctica lipase: Novozym 435

Racemic organoseleno-1-arylethanols were prepared by ortho-lithiation of arylethanols, followed by sequential reaction with elemental selenium and alkyl halides and by reaction of either aryldiazonium chlorides with diphenyldiselenide or with lithium and magnesium alkylselenolates. Enantiomerically enriched organoseleno-1-arylethanols were obtained by kinetic resolution of the racemic mixtures by esterification catalyzed by Candida antarctica lipase (Novozym 435). In some cases, enantiomeric excesses of up to 99% were obtained both for alcohols and acetates.     

Enzymatic kinetic resolution of ketorolac

Ketorolac 1 was resolved into each enantiomer by interesterification using lipase B from Candida antarctica. The acid reacted with various alcohols and the ester and acid were resolved up to >99% e.e. when reacted with octanol, which was the best result. To increase reactivity and enantioselectivity, the experimental conditions were adjusted by varying temperature, solvent, alcohols and reaction time.     

Lipase-catalyzed kinetic resolution of racemic 1-(10-alkyl-10H-phenothiazin-3-yl)ethanols and their butanoates

The synthesis of both enantiomers of 1-(10-alkyl-10H-phenothiazin-3-yl)ethanols and their butanoates by enantiomer-selective acylation of racemic alcohols with the lipase from Pseudomonas fluorescens (L-AK) or/and by methanolysis of the corresponding racemic esters with lipase B from Candida antarctica (CaL-B) is described. The absolute configuration of the enantiomerically pure enantiomers was determined by X-ray crystallography.     

Chemical and enzymatic synthesis of buprestin A and B—bitter acylglucosides from Australian jewel beetles (Coleoptera: Buprestidae)

A chemical and enzymatic synthesis was developed for buprestin A and B originally isolated from Australian jewel beetles (Coleoptera: Buprestidae). The common motif of both acylglucosides is a β-d-glucopyranose-1,2-bis(pyrrole-2-carboxylate). Starting from 1,3,4,6-tetra-O-acetyl-α-d-glucose, the first pyrrole-2-carboxylate was introduced by DCC-DMAP mediated esterification. After conversion to a trichloroacetimidate the anomeric pyrrole-2-carboxylate was installed. Selective removal of the acetates was accomplished using immobilized Candida antarctica lipase. The resulting triol was converted to Buprestin A or B via a Mitsunobu reaction.     

Enzymatic resolution of methyl N-alkyl-azetidine-2-carboxylates by Candida antarctica lipase-mediated ammoniolysis

A facile method for the synthesis of optically active azetidine-2-carboxylic acid derivatives is presented. Racemic N-alkylated azetidine esters are resolved by lipase from Candida antarctica in an ammoniolysis reaction, and both the S-amide and the R-ester are obtained with excellent stereoselectivity.     

A lipase catalyzed condensation reaction with a tricyclic diketone: yet another example of biocatalytic promiscuity

Novozym 435 (a commercially available immobilized form of Candida antarctica lipase B) was found to catalyze a condensation reaction of 5-hydroxy-endo-tricyclo[5.2.1.0^2,6]deca-4,8-dien-3-one with acetaldehyde (enzymatically produced from vinyl acetate in situ) under low water conditions, in presence of 10% organic co-solvent (N,N-dimethyl formamide or pyridine), to form a bis-adduct. Even though the condensation reaction occurred with pyridine (acting as a base catalyst) in the presence of acetaldehyde and in the absence of enzyme, the reaction was very slow as compared to the enzymatic process. Thus, while the non-enzymatic process took 4 days to achieve 100% conversion; in presence of enzyme it was possible within 4 h.     

Synthesis of Geraniol Esters in a Continuous-Flow Packed-Bed Reactor of Immobilized Lipase: Optimization of Process Parameters and Kinetic Modeling

With increasing demand for perfumes, flavors, beverages, and pharmaceuticals, the various associated industries are resorting to different approaches to enhance yields of desired compounds. The use of fixed-bed biocatalytic reactors in some of the processes for making fine chemicals will be of great value because the reaction times could be reduced substantially as well as high conversion and yields obtained. In the current study, a continuous-flow packed-bed reactor of immobilized Candida antarctica lipase B (Novozym 435) was employed for synthesis of various geraniol esters. Optimization of process parameters such as biocatalyst screening, effect of solvent, mole ratio, temperature and acyl donors was studied in a continuous-flow packed-bed reactor. Maximum conversion of ~ 87% of geranyl propionate was achieved in 15 min residence time at 70 °C using geraniol and propionic acid with a 1:1 mol ratio. Novozym 435 was found to be the most active and stable biocatalyst among all tested. Ternary complex mechanism with propionic acid inhibition was found to fit the data.     

Lipase-mediated enantioselective acylation of alcohols with functionalized vinyl esters: acyl donor tolerance and applications

Enzymatic acylation is commonly used for the kinetic resolution of alcohols and amines. The simple acyl group introduced during the enzymatic reaction is usually removed or replaced by another group. Retention of more complex acyl moieties as part of the target structures would be a more efficient strategy. We have studied the enantioselective acylation of a model alcohol substrate, 1-phenylethanol, with vinyl esters bearing various functionality on the acyl moieties in the presence of three lipases (Candida antarctica, Candida rugosa and Burkholderia cepacia) frequently used in organic synthesis. C. antarctica lipase is the most versatile lipase for this type of biotransformations. We applied this strategy to the synthesis of a protein kinase C ligand and a natural product, phoracantholide.     

A novel lipase enzyme panel exhibiting superior activity and selectivity over lipase B from Candida antarctica for the kinetic resolution of secondary alcohols

A novel, commercially available lipase enzyme panel performing kinetic bioresolutions of a number of secondary alcohols is reported. The secondary alcohols that have been chosen are known from the literature to be particularly challenging substrates to resolve. Following initial screening, four co-solvents were investigated for each lead enzyme in an effort to assess their tolerance to common organic solvents. The superiority of these novel enzymes over lipase B from Candida antarctica (CALB) has been demonstrated.     

Enzyme-mediated enantioselective hydrolysis of soluble polymer-supported carboxylates

The enzyme-mediated enantioselective hydrolysis of water-soluble polymer-supported carboxylates is disclosed. The representative monomethoxy poly(ethylene glycol) (MPEG, av MW 5000)-supported substrate was synthesized by immobilization of (±)-1-phenylethanol onto the modified MPEG (MPEG/NH₂) through an carboxylate linker with a succinate spacer. For the screening of the hydrolytic enzymes, the substrate was enantioselectively hydrolyzed by lipase from Candida antarctica (Novozym 435) in a mixed solvent (hexane/buffer=9/1) at 30 °C to afford the remaining (S)-substrate and the resulting (R)-alcohol (E value>200). The products were easily separated by a simple procedure without any laborious column chromatography. The substrate was hydrolyzed with NaOH in MeOH/H₂O to afford the corresponding (S)-alcohol. We also found that the structure of the spacer between the MPEG moiety and the carboxylate linker strongly affected both the reactivity and enantioselectivity, and the substrate bearing a glutarate spacer gave the best result. Our procedure was applicable for the preparation of several optically active alcohols.     

Enzymatic procedure catalysed by lipase from Candida antarctica for the regioprotection–deprotection of glucosamine

Both peracetyl α-glucosamine 3 and its β-epimer 4 undergo alcoholysis with butanol in THF, catalysed by lipase from Candida antarctica (Novozym 435) to afford the triester 6 and diester 9, respectively. Esterification of these compounds, using vinyl acetate in the presence of Novozym 435, gives the partial esters 10 and 11, bearing a deprotected hydroxyl function at C-4, ready for inversion of configuration to open a route in the preparation of galactosamine.     

Chemical constituents from Piper marginatum Jacq. (Piperaceae)—antifungal activities and kinetic resolution of (RS)-marginatumol by Candida antarctica lipase (Novozym 435)

The leaves of Piper marginatum contain the antifungal compounds 3,4-methylenedioxypropiophenone 1, 2-methoxy-4,5-methylenedioxypropiophenone 2, 1-(3,4-methylenedioxyphenyl)propan-1-ol 3 (marginatumol), 5,4′-dihydroxy-7-methoxyflavanone 4 and 5,7-dihydroxy-4′-methoxyflavanone 5. The absolute configuration of natural marginatumol was determined as (+)-(R)-3 (ee 48%) by comparison of its optical properties with the chiral forms obtained by kinetic resolution of racemic 3 using Candida antarctica lipase (Novozym 435).