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.
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).
Lecitase™ Ultra was immobilized on four different supports and tested for the first time as the biocatalyst in the kinetic resolution of racemic allyl alcohols with the (E)-4-arylbut-3-en-2-ol system in the process of transesterification. The most effective biocatalyst turned out to be the enzyme immobilized on agarose activated with cyanogen bromide (LU-CNBr). The best results (E > 200, ees and eep = 95–99%) were obtained for (E)-4-phenylbut-3-en-2-ol and its analog with a 2,5-dimethylphenyl ring whereas the lowest ee of kinetic resolution products (90%) was achieved for the substrate with a 4-methoxyphenyl substituent. For all substrates, (R)-enantiomers were esterified faster than their (S)-antipodes. The results showed that LU-CNBr is a versatile biocatalyst, showing high activity and enantioselectivity in a wide range of organic solvents in the presence of commonly used acyl donors. High operational stability of LU-CNBr allows it to be reused in three subsequent reaction cycles without negative effects on the efficiency and enantioselectivity of transesterification. This biocatalyst can become attractive to the commercial lipases in the process of the kinetic resolution of allyl alcohols.
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