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

Abstract

The influence of buffer type, co-solvent type, and acyl chain length was investigated for the enantioselective hydrolysis of racemic 4-arylbut-3-en-2-yl esters using Lecitase™ Ultra (LU). Immobilized preparations of the Lecitase™ Ultra enzyme had significantly higher activity and enantioselectivity than the free enzyme, particularly for 4-phenylbut-3-en-2-yl butyrate as the substrate. Moreover, the kinetic resolution with the immobilized enzyme was achieved in a much shorter time (24–48 h). Lecitase™ Ultra, immobilized on cyanogen bromide-activated agarose, was particularly effective, producing, after 24 h of reaction time in phosphate buffer (pH 7.2) with acetone as co-solvent, both (R)-alcohols and unreacted (S)-esters with good to excellent enantiomeric excesses (ee 90–99%). These conditions and enzyme were also suitable for the kinetic separation of racemic (E)-4-phenylbut-3-en-2-yl butyrate analogs containing methyl substituents on the benzene ring (4b,4c), but they did not show any enantioselectivity toward (E)-4-(4’-methoxyphenyl)but-3-en-2-yl butyrate (4d).

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

“…Noteworthy is the significantly shorter time (6-8 h) needed for effective separation of alcohols 1b and 1c by transesterification compared to the hydrolysis of their butyrates (24-48 h) [34]. In contrast to the non-enantioselective hydrolysis of butyrate containing a methoxy substituent on a benzene ring [34], transesterification of alcohol bearing this substituent (1d) was enantioselective and it was possible to obtain both products with relatively high enantiomeric excess.…”

“…Racemic alcohols 1a-d were synthesized from corresponding aromatic aldehydes as described In our previous studies on the hydrolysis of (E)-4-arylbut-3-en-2-yl esters, a similar effect of the substituents on the benzene ring on the activity and enantioselectivity of the reaction catalyzed by LU-CNBr has been shown [34]. Similar to the hydrolysis reaction, the best resolution in the process of transesterification was observed for substrates with unsubstituted benzene ring and with a 2,5-dimethylphenyl substituent; very good results were also obtained for compounds with a p-methylphenyl substituent.…”

“…Similar to the hydrolysis reaction, the best resolution in the process of transesterification was observed for substrates with unsubstituted benzene ring and with a 2,5-dimethylphenyl substituent; very good results were also obtained for compounds with a p-methylphenyl substituent. Noteworthy is the significantly shorter time (6-8 h) needed for effective separation of alcohols 1b and 1c by transesterification compared to the hydrolysis of their butyrates (24-48 h) [34]. In contrast to the non-enantioselective hydrolysis of butyrate containing a methoxy substituent on a benzene ring [34], transesterification of alcohol bearing this substituent (1d) was enantioselective and it was possible to obtain both products with relatively high enantiomeric excess.…”

“…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.…”