Whole cell application of Lactobacillus paracasei BD101 to produce enantiomerically pure (S)‐cyclohexyl(phenyl)methanol

Abstract

In this study, a total of 10 bacterial strains were screened for their ability to reduce cyclohexyl(phenyl)methanone 1 to its corresponding alcohol. Among these strains, Lactobacillus paracasei BD101 was found to be the most successful biocatalyst to reduce the ketones to the corresponding alcohols.The reaction conditions were systematically optimized for the reducing agent L paracasei BD101, which showed high enantioselectivity and conversion for the bioreduction. The preparative scale asymmetric reduction of cyclohexyl(phenyl)methanone (1) by L paracasei BD101 gave (S)cyclohexyl(phenyl)methanol (2) with 92% yield and >99% enantiomeric excess. The preparative scale study was carried out, and a total of 5.602 g of (S)-cyclohexyl(phenyl)methanol in high enantiomerically pure form (>99% enantiomeric excess) was produced. L paracasei BD101 has been shown to be an important biocatalyst in asymmetric reduction of bulky substrates. This study demonstrates the first example of the effective synthesis of (S)-cyclohexyl(phenyl)methanol by the L paracasei BD101 as a biocatalyst in preparative scale.

Biocatalyzed Enantiomerically Pure Production of (S)‐Phenyl(thiophen‐2‐yl)methanol

“…At the end of the experiment using 30‐mmol substrates, it was observed that the conversion was completed after 62 h, but the ee of the product was very low (81%). This could be due to the reduction in the enzyme activity, suggesting substrate toxicity and inhibition as reported previously . Based on this knowledge, the substrate concentration was investigated with slight changes.…”

“…This can be explained by the change of the three‐dimensional structure of the enzyme with the change of pH and interaction of the active center of the enzyme with the substrate, especially the S atom on the substrate. In addition, in the biotransformation process, the substrate should be able to pass through the cell membrane; therefore, selectivity could be changed as it would alter the solubility of the substrate by pH change . The highest conversion (82%) with 88% ee was obtained when the pH was at 6.5.…”

“…When the amount of dry biocatalyst is 40 and 60 mg, the ee decreases to 82 and 77%, respectively. This can be attributed to the alteration of the amount of NADPH in the medium, which can affect the selectivity, and so, activity of the enzyme may have changed . In order to obtain large‐scale products and high selectivity, asymmetric reduction reactions using biocatalysts are particularly important for chiral secondary alcohols, which cannot be obtained in large quantities with chemical catalysts.…”

“…Recently, we performed asymmetric reduction of acetophenones, piperonyl methyl ketone, and cyclohexyl(phenyl)methanone by high enantioselectivity and conversion using Lactobacillus paracasei BD101 as biocatalyst .…”

Whole‐cell biocatalytic of Bacillus cereus WZZ006 strain to synthesis of indoxacarb intermediate: (S)‐5‐Chloro‐1‐oxo‐2,3‐dihydro‐2‐hydroxy‐1H‐indene‐2‐carboxylic acid methyl ester

“…The whole cell biocatalytic synthesis has continually emerged as an outstanding method to replace traditional chemical methods in some fields . Few bacterial strains like, Lactobacillus paracasei BD101 were used as whole cell biocatalyst for pure ( S )‐cyclohexyl (phenyl)methanol . Also, Vitale et al used Lactobacillus reuteri DSM 20016 whole cells for the production of ( S )‐rivastigmine.…”