Synthesis of Enantiomerically Enriched Drug Precursors by Lactobacillus paracasei BD87E6 as a Biocatalyst

Abstract

Global sales of single enantiomeric drug products are growing at an alarming rate every year. A total of 7 bacterial strains were screened for their ability to reduce acetophenones to its corresponding alcohol. Among these strains Lactobacillus paracasei BD87E6 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 Lactobacillus paracasei BD87E6, which showed high enantioselectivity and conversion for the bioreduction. The preparative scale asymmetric reduction of 3‐methoxyacetophenone (1h) by Lactobacillus paracasei BD87E6 gave (R)‐1‐(3‐methoxyphenyl)ethanol (2h) with 92% yield and 99% enantiomeric excess. Compound 2h could be used for the synthesis of (S)‐rivastigmine which has a great potential for the treatment of Alzheimer's disease. This study demonstrates that Lactobacillus paracasei BD87E6 can be used as a biocatalyst to obtain chiral carbinol with excellent yield and selectivity. The whole cell catalyzed the reductions of ketone substrates on the preparative scale, demonstrating that Lactobacillus paracasei BD87E6 would be a valuable biocatalyst for the preparation of chiral aromatic alcohols of pharmaceutical interest.

Impact of Gut Microbiome Lactobacillus spp. in Brain Function and its Medicament towards Alzheimer’s Disease Pathogenesis

“…The gut microbiota consists of numerous bacterial species dwelling inside the gastrointestinal tract (GIT) existing as symbionts with the human host 16 and is believed to play an essential role in physiology 17,18 . A 51% of gut microbiota are belonging to the Firmicutes phyla comprising the groups of Clostridium coccoides and Clostridium leptum and the most acknowledged Lactobacillus genera and 48% consists of the Bacteroidetes phyla comprising well recognized genera of Prevotella and Bacteroides 19,20 . The remaining 1% of microbiota is the less-known phyla, comprising Proteobacteria, Actinobacteria, Bifidobacteria, Fusobacteria, Spirochaetes, Verrucomicrobia, and Lentispaerae 19,21 .…”

“…L. plantarum MTCC 1325 was reported to produce acetylcholine (Ach) neurotransmitter which has properties against D-galactose induced AD impairment 1 . L. paracasei BD87E6 was reported to produce (S)-rivastigmine, an anticholinesterase inhibitor that serves the cholinergic hypothesis 20 . A dysregulation in the gut microbiota can lead to AD by regulating short-chain fatty acid (SCFA) 53 .…”

Revisitation of the Preparation of (S,S)‐2,8‐Diazabicyclo[4.3.0]nonane Through Enzymatic Resolution.

“…Enzymes play a crucial role in green chemistry as they function as catalysts, accelerating chemical reactions without requiring harsh reaction conditions or chemicals, and are also reusable. [6][7][8][9][10][11][12][13][14] A chemo-enzymatic strategy via kinetic resolution of cis-(�)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate (cis-13) has been claimed in a patent by FIS Italian Factory Synthetic SPA (Scheme 4). [15] It involves the use of covalently immobilized lipase B from Candida antarctica (CAL B).…”

“…In view of green chemistry aspects, biocatalytic approaches have been developed as an alternative to chemical resolution. Enzymes play a crucial role in green chemistry as they function as catalysts, accelerating chemical reactions without requiring harsh reaction conditions or chemicals, and are also reusable [6–14] . A chemo‐enzymatic strategy via kinetic resolution of cis ‐(±)‐dimethyl 1‐acetylpiperidine‐2,3‐dicarboxylate ( cis ‐ 13 ) has been claimed in a patent by FIS Italian Factory Synthetic SPA (Scheme 4).…”

Green and scalable synthesis of chiral aromatic alcohols through an efficient biocatalytic system

“…Biocatalysis can be performed by using whole‐cell microorganism or isolated enzymes as both methods have some advantages and drawbacks (Öksüz et al ., 2018). Whole‐cell biocatalysts are easy to obtain and relatively cheap and more stable, but its catalytic reaction is subject to the influence of other metabolic reactions in the cell, which produce other by‐products, affecting the separation and purification of the target products (Şahin, 2019).…”