Modified distance optimization method for the asymmetric bioreduction conditions of phenyl(thiophen-2-yl)methanone by Weissella paramesenteroides N7

• Published in: Tetrahedron 2023-06, Vol.139, p.133431, Article 133431
• Main Authors: Özdemir, Akın, Şahin, Engin
• Format: Article
• Language: English
• Subjects: Asymmetric bioreduction; Biocatalyst; Chiral carbinol; Green synthesis; Modified distance optimization
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2023.133431

Chirality plays a significant part in life since it is closely linked to carrying out the many metabolic processes that make up a living being. Chiral secondary alcohols such as diaryl-, aryl heteroaryl-, and diheteroaryl are employed in pharmaceuticals as drug intermediates. Although biocatalytic asymmetric reduction of prochiral ketones containing aromatic and heteroaromatic groups is widely known, biocatalytic reduction of heteroaromatic prochiral ketones containing sulfur heteroatoms is rarely known. Very few studies exist in the literature, including the biocatalytic reduction of phenyl(thiophen-2-yl)methanone (1). Moreover, the biocatalytic reduction of 1 with a mathematical modelling and optimization technique is unknown until now. In this study, Weissella paramesenteroides N7 biocatalyst for the asymmetric bioreduction of 1 using a novel modified distance optimization method. Optimization conditions were found as pH = 6.46, temperature = 26 °C, incubation period = 71 h, agitation speed = 200 rpm by the modified distance optimization method, and it was determined that the conversion and enantiomeric excess (ee) under these conditions could be 98.7% and 98%, respectively. Under these proposed optimization conditions, (S)-phenyl(thiophen-2-yl)methanol ((S)-2) was obtained with >99% ee, >99% conversion, and 97% yield. In addition, 11.29 g of 1 was completely converted into (S)-2 (11.07 g, 97% isolated yield) under optimized conditions. This is the first report about the fabrication of enantiopure (S)-2 in high gram scale using a biocatalyst and a novel modified distance optimization technique. In this study, the successful applicability of the new modified distance optimization method in biocatalytic asymmetric reduction reactions has been successfully demonstrated. [Display omitted] •The reduced quadratic models were obtained for the ee and cr response functions.•A modified distance optimization method was developed for asymmetric reactions.•The optimum conditions were found for the specified culture factors.•The ee, conversion, and yield were obtained as 99%, 99%, and 97%, respectively.•Weissella paramesenteroides N7 can be used as a biocatalyst.