Application of Lecitase® Ultra-Catalyzed Hydrolysis to the Kinetic Resolution of (E)-4-phenylbut-3-en-2-yl Esters

Abstract

The possibility of using Lecitase® Ultra as a novel alternative biocatalyst for the kinetic resolution of model racemic allyl esters of (E)-4-phenylbut-3-en-3-ol: Acetate (4a) and propionate (4b) through their enantioselective hydrolysis was investigated. Reaction afforded (+)-(R)-alcohol (3) and unreacted (−)-(S)-ester (4a or 4b). Hydrolysis of propionate 4b proceeded with higher enantioselectivity than acetate 4a. (R)-Alcohol (3) with highest enantiomeric excess (93–99%) was obtained at 20–30 °C by hydrolysis of propionate 4b, while the highest optical purity of unreacted substrate was observed for (S)-acetate 4a (ee = 34–56%). The highest enantioselectivity was found for the hydrolysis of propionate 4b catalyzed at 30 °C (E = 38). Reaction carried out at 40 °C significantly lowered enantiomeric excess of produced alcohol 3 and enantioselectivity in resolution. Lecitase® Ultra catalyzed the enantioselective hydrolysis of allyl esters 4a,b according to Kazlauskas’ rule to produce (R)-alcohol 3 and can find application as a novel biocatalyst in the processes of kinetic resolution of racemic allyl esters.

Free and Immobilized Lecitase™ Ultra as the Biocatalyst in the Kinetic Resolution of (E)-4-Arylbut-3-en-2-yl Esters

“…Similarly, in our earlier work, CALB was used to resolve racemic acetate 2a and propionate 3a in the reaction conditions analogous to those used in this study. A short time was needed to achieve kinetic resolution (6 h and 2 h, respectively), but significantly lower enantiomeric excess of unreacted ester was observed (80-85%) [60]. In other work, Thalén et al [66] used CALB in the hydrolysis of enantiomerically enriched (S,E)-4-phenylbut-3-en-2-yl butyrate (ee 95%) to obtain optically pure butyrate 4a after 2 h of reaction carried out in a phosphate buffer (pH 7.2), but the reaction was carried out at high temperature (60 • C).…”

“…The extracts were dried and solvent was removed by evaporation in vacuo. Before chiral gas chromatography (CGC) samples taken from the reaction mixture were treated with propionyl or acetyl chloride to derivatize inseparable enantiomers of alcohols 1a-d into the corresponding esters as described earlier [60].…”

“…In our previous paper, we reported the preliminary results of the free Lecitase™ Ultra-mediated kinetic resolution of model racemic esters of (E)-4-phenylbut-3-en-2-ol through their enantioselective hydrolysis, achieving moderate to good enantiopurity of the products [60]. Here, we present the results of our further investigations in this field, aiming to increase the process efficacy through optimization of some reaction conditions (pH of the reaction medium, addition of organic co-solvent) as well as by enzyme immobilization.…”

Enantioselective Transesterification of Allyl Alcohols with (E)-4-Arylbut-3-en-2-ol Motif by Immobilized Lecitase™ Ultra

“…LU was also successfully applied to the modifications of acyl chains in phospholipids by acidolysis or transesterification with fatty acids or their esters, respectively [25][26][27][28]. In the area of asymmetric synthesis, it was used for the enantioselective hydrolysis of some racemic mixtures, including mandelic acid derivatives [29], glycidate esters [30,31], α-aminoacids [32], and 4-arylbut-3-en-2-yl esters [33,34].…”

“…These alcohols can be obtained by the enzymatic resolution of racemic mixtures. In our previous papers, we reported a free and immobilized Lecitase TM Ultra-catalyzed kinetic resolution of (E)-4-arylbut-3-en-2-yl esters via their enantioselective hydrolysis [33,34]. Taking into consideration the activity of LU towards the synthesis of flavor esters by esterification or transesterification of alcohols [39,55,61], in this work we decided to employ LU for the kinetic resolution of racemic alcohols with the 4-arylbut-3-en-2-ol system in the process of transesterification.…”