Öksüz Selda, Şahin Engin, Dertli Enes
Department of Food Engineering, Faculty of Engineering, Bayburt University, Bayburt, 69000, Turkey.
Chem Biodivers. 2018 Jun;15(6):e1800028. doi: 10.1002/cbdv.201800028. Epub 2018 May 24.
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.
单一对映体药物产品的全球销售额每年都在以惊人的速度增长。总共筛选了7种细菌菌株还原苯乙酮生成相应醇的能力。在这些菌株中，副干酪乳杆菌BD87E6被发现是将酮还原为相应醇的最成功的生物催化剂。对还原剂副干酪乳杆菌BD87E6的反应条件进行了系统优化，该菌株在生物还原反应中表现出高对映选择性和转化率。副干酪乳杆菌BD87E6对3-甲氧基苯乙酮（1h）进行制备规模的不对称还原反应，得到（R）-1-（3-甲氧基苯基）乙醇（2h），产率为92%，对映体过量为99%。化合物2h可用于合成（S）-卡巴拉汀，其在治疗阿尔茨海默病方面具有巨大潜力。这项研究表明，副干酪乳杆菌BD87E6可作为生物催化剂，以优异的产率和选择性获得手性甲醇。全细胞在制备规模上催化了酮底物的还原反应，表明副干酪乳杆菌BD87E6将是制备具有药学意义的手性芳香醇的有价值的生物催化剂。
