Acylation Step (acylation + step)

Distribution by Scientific Domains

Selected Abstracts

Stereoselective Hydrolysis of Quaternary Quinuclidinium Benzoates Catalyzed by Butyrylcholinesterase

Ines Primoz
Abstract Four chiral, quaternary, N -methyl and N -benzyl derivatives of (R)- and (S)-quinuclidin-3-yl benzoates were synthesized and studied as substrates of horse serum butyrylcholinesterase (BChE). The kcat for the substrates decreased in the order (R)- N -methyl > (R)- N -benzyl (2.3-fold slower) >> (S)- N -methyl (70.5-fold slower reaction), while for the (S)- N -benzyl ester inhibition of the enzyme was observed. The kinetics of inhibition (Ka = 3.3 ,M) indicated that binding to the catalytic site of BChE occurred. From the ratio of the kcat/KM values of both enantiomers an enantiomeric excess of 95% was calculated for N -methyl derivatives. Thus, BChE is suitable as a biocatalyst for the resolution of racemic quaternary quinuclidinium esters. In order to explain the experimental data, combined quantum chemical (HF/3,21G*) and semiempirical (PM3) calculations within the ONIOM scheme of the stable species in the acylation step were performed. Geometry optimizations were carried out for all benzoate esters for an assumed active site model of BChE. It was confirmed that hydrolysis is affected to an appreciable extent by a proper geometrical orientation of substrates at the choline subsite. The energies of the optimized systems were in good agreement with the experimental data. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source]

(R,S)-Azolides as Novel Substrates for Lipase-Catalyzed Hydrolytic Resolution in Organic Solvents

Pei-Yun Wang
Abstract Azolides, that is, N -acylazoles, as versatile acylation reagents are well characterized in the literature, in which the azole structure can not only act as a better leaving group but also make the carbonyl carbon more electrophilic and susceptible to nucleophilic attack. It is therefore desirable to combine this unique property and lipase resolution ability in the development of a new resolution process for preparing optically pure carboxylic acids. With the Candida antarctica lipase B (CALB) - catalyzed hydrolysis of (R,S)- N -profenylazoles in organic solvents as the model system, (R,S)- N -profenyl-1,2,4-triazoles instead of their corresponding ester analogues were exploited as the best substrates for preparing optically pure profens, i.e., 2-arylpropionic acids. The structure-reactivity correlations for the (R,S)-azolides in water-saturated methyl tert -butyl ether (MTBE) at 45,C coupled with a thorough kinetic analysis were further employed for elucidating the rate-limiting formation of a tetrahedral adduct without CN bond breaking or with moderate CN bond breaking concerted with CO bond formation in the acylation step. The advantages of easy substrate preparation, high enzyme reactivity and enantioselectivity, and easy recovery of the product and remaining substrate by aqueous extraction demonstrate the potential of using (R,S)-azolides as novel substrates for the enzymatic resolution process. [source]

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

Chun-Chi Chen
Abstract 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. 2006 Wiley Periodicals, Inc. [source]