Lipase-catalyzed enantioselective resolution of (R,S)-N-2-methylalkanoyl-3-(2-pyridyl)pyrazoles in organic solvents

Enzyme Promiscuity as a Remedy for the Common Problems with Knoevenagel Condensation

“…When the water content was low,t he conformation of PPL was excessively rigid, which made the "induced-fit"p rocess of PPLd ifficult andl ed to the low enzymea ctivity.H owever,t he enzymec onformation in organic media with high water content mayb et oo flexible, which may also decrease the activity of the enzyme. [31] The obtained results reveal that acertain amount of water is obligatory and that the molecular water present in the enzymes tructure is insufficient for the studied tandeme nzymatic transformation. Interestingly,t he yield of the product 3a decreased with elevationo ft he temperature, reaching 46 %a t4 0 8C (entry 5).…”

One-pot chemo- and photo-enzymatic linear cascade processes

“…This strategy represents an important advancement compared to the conventional methods to prepare these challenging compounds, which is mainly based on kinetic resolutions (inherently limited to 50% maximum yield) or asymmetric hydrogenation of α,β-carboxylic acids, leading to moderate enantioselectivities and lower yields. 174,175 Interesting chemo-enzymatic processes performed by combining C–C bond forming reactions with enzymes have also been reported for the synthesis of carboxylic acids. Thus, Gröger et al 176 reported a new synthetic process for the preparation of cyclic malonic acid monoesters, which are of interest as intermediates for the preparation of non-natural amino acids bearing a quaternary carbon center.…”

Kinetic and Thermodynamic Investigation of Lipase-Catalyzed Hydrolysis of (R,S)-3-Phenylbutyl Azolides

“…From the logarithm of enantiomeric ratio varied with the inverse of absolute temperature, i.e., R ln­( E ) = −ΔΔ H / T + ΔΔ S , coupled with the data in Table , −ΔΔ H , and −ΔΔ S defined as differences of enthalpy and entropy between the transition states for both enantiomers are estimated . The results and others estimated from lipase-catalyzed resolution of ( R , S )-azolides containing an α-chiral center are tabulated in Table S2 of the Supporting Information.…”

“…Lipases are widely employed as versatile biocatalysts for preparing chiral alcohols, amines, and carboxylic acids as the intermediates for synthesizing a variety of pharmaceuticals and fine chemicals. , In comparison with the kinetic resolution of secondary alcohols and amines, the enzyme enantioselectivity toward carboxylic acids is usually low to modest, due to few or weaker contacts between the acyl part and its binding site. − Recently, a lipase-catalyzed resolution process for ( R , S )-azolides, i.e., ( R , S )- N -acylazoles, but not their corresponding ester or normal amide analogues was reported for preparing optically pure carboxylic acids containing an α-chiral center. − The results indicate that by carefully selecting the leaving azole moiety, the enzyme activity and enantioselectivity may greatly improve. This can be attributed to the unique azolide structure that contains unshared electron pairs on the acyl-substituted nitrogen N(1), making the carbonyl carbon atom more electrophilic and susceptible to nucleophilic attack and breakage of the leaving azole moiety, especially when accepting a proton from the imidazolium of catalytic histidine.…”