A study of the enantiopreference of lipase PS (Pseudomonas cepacia) towards diastereomeric dihydro-5-alkyl-4-hydroxymethyl-2(3H)-furanones

Berti, Federico; Forzato, Cristina; Nitti, Patrizia; Pitacco, Giuliana; Valentin, Ennio

doi:10.1016/j.tetasy.2005.01.036

Cited by 10 publications

(11 citation statements)

References 72 publications

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“…[32][33][34] Representative examples of lipases used for acyl transfer are lipase from P. cepacia (Amano PS), lipase-B from Candida antarctica (CAL-B), Candida rugosa (CRL), and P. fluorescens (PFL). [48][49][50][51][52][53][54][55][56][57][58][59] Several strategies have been attempted to overcome this, such as the use of chiral or sterically demanding acyl donors, 56,60 optimization of solvation conditions, 61 or through sequential resolutions. [48][49][50][51][52][53][54][55][56][57][58][59] Several strategies have been attempted to overcome this, such as the use of chiral or sterically demanding acyl donors, 56,60 optimization of solvation conditions, 61 or through sequential resolutions.…”

Section: Introductionmentioning

confidence: 99%

1‐Hydroxymethyl‐7‐oxabicyclo[2.2.1]hept‐2‐ene skeleton in enantiopure form through enzymatic kinetic resolution

Reddy

Manheri

2019

Chirality

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Lipase-catalysed enantioselective acetylation and deacetylation routes were investigated to prepare 1,5,6-trisubstituted 7-oxabicyclo[2.2.1]hept-2-ene skeleton in enantio-pure form. The racemic alcohol (6) used in acetylation reaction was accessed through Diels-Alder reaction of TBDMS-protected furfuryl alcohol with maleic anhydride, followed by reduction-benzylation-desilylation sequence. After systematic screening of lipases and solvents, Candida antarctica B on acrylic resin in pentane was identified as the best system that gave >98% ee towards the (+) acetate with 40% conversion, in 30 minutes. Absolute stereochemistry of this product was confirmed by X-ray diffraction analysis of its 3,5-dinitrobenzoate derivative (9). Enantioselective deacetylation of the racemic acetate of this starting material was then studied with the same set of lipases. After various optimization studies, Candida antarctica B in toluene as the solvent was found to be the most effective that gave 49% conversion with >99% ee towards the (+)-alcohol (8) at the end of 18 hours.

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Section: Introductionmentioning

confidence: 99%

1‐Hydroxymethyl‐7‐oxabicyclo[2.2.1]hept‐2‐ene skeleton in enantiopure form through enzymatic kinetic resolution

Reddy

Manheri

2019

Chirality

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“…(B) BCL favors the 4R enantiomer with no reversal enantiopreference for the cis (11 and 12) and trans (14) compounds. [24] The configuration of the g-substituent in the favored enantiomer differs for the trans (5R) and cis (5S) compounds. BCL shows no enantioselectivity for compound 13 and the highest enantioselectivity (E = 150) toward 12-acetate.…”

Section: Introductionmentioning

confidence: 99%

“…[10,24,31,[33][34][35][36][37][38] One difficulty is that the fast-reacting enantiomers bind differently depending on the substrate. Large, non-polar substituents bind to either the HH or HA pocket and medium-sized non-polar substituents also bind to different regions.…”

Section: Introductionmentioning

confidence: 99%

Molecular Basis for the Enantio‐ and Diastereoselectivity of Burkholderia cepacia Lipase toward γ‐Butyrolactone Primary Alcohols

Eum

Kazlauskas

2014

Adv Synth Catal

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Burkholderia cepacia lipase (BCL) shows high enantioselectivity toward chiral primary alcohols, but this enantioselectivity is often unpredictable, especially for substrates that contain an oxygen at the stereocenter. For example, BCL resolves bsubstituted-g-acetyloxymethyl-g-butyrolactones (acetates of a chiral primary alcohol) by hydrolysis of the acetate, but the enantioselectivity varies with the nature and orientation of the b-alkyl substituent. BCL favors the (R)-primary alcohol when the balkyl substituent is hydrogen (E = 30) or trans methyl (E = 38), but the (S)-primary alcohol when it is cis methyl (E = 145). To rationalize this unusual selectivity, we used a combination of experiments to show the importance of polar interactions and modeling to reveal differences in orientations of the enantiomers. Removal of either the lactone carbonyl in the substrate or the polar side chains in the enzyme by using a related enzyme without these side chains decreased the enantioselectivity at least four-fold. Modeling revealed that the slow enantiomers do not bind by exchanging the location of two substituents relative to the fast enantiomer. Instead, three substituents remain in the same region, but the fourth substituent, hydrogen, inverts to a new location, like an umbrella in a strong wind. In this orientation the favored stereoisomers have similar shapes, thus accounting for the unusual stereoselectivity. The ratio of catalytically productive orientations for the fast vs. slow enantiomers in a molecular dynamic simulation correlated (R 2 = 0.82) with the degree of enantioselectivity including the case where the enantioselectivity reversed. Weighting this ratio by the ratio of Hbonds in the polar interaction to account for different binding strengths improved the correlation with the measured enantioselectivity to R 2 = 0.97. The modeling identifies key interactions responsible for high enantioselectivity in this class of substrates.

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“…There are some studies on this aspect, for example, there are two distinct modeling strategies for predicting lipase activity highlights: structure-based approach and data-driven approach. The structure-based models start with a known active site structure of the lipase [17-19] and then identify the preferred substrates based on conformation, charge, and other force field calculations [20,21]. On the other hand, data driven models such as quantitative structure–activity relationship (QSAR) approach develops a mathematical relationship between the enzyme activity and structural descriptors of substrates using available experimental data.…”

Section: Introductionmentioning

confidence: 99%

QSAR study and the hydrolysis activity prediction of three alkaline lipases from different lipase-producing microorganisms

Wang

et al. 2012

Lipids Health Dis

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The hydrolysis activities of three alkaline lipases, L-A1, L-A2 and L-A3 secreted by different lipase-producing microorganisms isolated from the Bay of Bohai, P. R. China were characterized with 16 kinds of esters. It was found that all the lipases have the ability to catalyze the hydrolysis of the glycerides, methyl esters, ethyl esters, especially for triglycerides, which shows that they have broad substrate spectra, and this property is very important for them to be used in detergent industry. Three QSAR models were built for L-A1, L-A2 and L-A3 respectively with GFA using Discovery studio 2.1. The models equations 1, 2 and 3 can explain 95.80%, 97.45% and 97.09% of the variances (R2adj) respectively while they could predict 95.44%, 89.61% and 93.41% of the variances (R2cv) respectively. With these models the hydrolysis activities of these lipases to mixed esters were predicted and the result showed that the predicted values are in good agreement with the measured values, which indicates that this method can be used as a simple tool to predict the lipase activities for single or mixed esters.

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A study of the enantiopreference of lipase PS (Pseudomonas cepacia) towards diastereomeric dihydro-5-alkyl-4-hydroxymethyl-2(3H)-furanones

Cited by 10 publications

References 72 publications

1‐Hydroxymethyl‐7‐oxabicyclo[2.2.1]hept‐2‐ene skeleton in enantiopure form through enzymatic kinetic resolution

1‐Hydroxymethyl‐7‐oxabicyclo[2.2.1]hept‐2‐ene skeleton in enantiopure form through enzymatic kinetic resolution

Molecular Basis for the Enantio‐ and Diastereoselectivity of Burkholderia cepacia Lipase toward γ‐Butyrolactone Primary Alcohols

QSAR study and the hydrolysis activity prediction of three alkaline lipases from different lipase-producing microorganisms

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