Tozlu, NesrullahBulbul, Ali SavasOzdemir, AkinSahin, Engin2024-10-042024-10-0420232468-8231https://doi.org/10.1016/j.mcat.2023.113404http://hdl.handle.net/20.500.12403/3254Asymmetric bioreductions catalyzed by biocatalysts have demonstrated great promise in manufacturing chiral alcohols. On the other hand, the synthesis of (S)-(4-chlorophenyl)(phenyl)methanol ((S)-2), precursors of Lcloprastine and carbinoxamine, still presents considerable challenges due to the inadequate substrate quantity and production process. In this work, a novel rotatable composite design-based optimization technique was used with the Lactobacillus paracasei BD101 biocatalyst for the asymmetric reduction of (4-chlorophenyl)(phenyl) methanone (1). Optimization conditions of the reaction were determined by the proposed optimization strategy as: pH=5.85, temperature=37 degrees C, incubation time=71 h, and agitation speed=120 rpm. The reaction conversion and the product of enantiomeric excess (ee) were also predicted to be 97% and 99%, respectively. In the experimental study performed under the determined optimized conditions, (S)-2 was obtained with >99% ee, >99% conversion, and 97% yield. In addition, 1 with the amount of 15.166 g was completely converted to (S)-2 (14.85 g, 97% isolated yield) on a high-gram scale. Notice that the manufacture of (S)-2 on a gram scale utilizing a biocatalyst and an optimization technique is demonstrated in this work for the first time. Finally, an economical, effective, and environmentally friendly biocatalytic process for the biocatalytic synthesis of (S)-2, which have antitussive and antiemetic properties and relax the bronchial muscle, has been demonstrated by the novel rotatable composite design-based optimization method.eninfo:eu-repo/semantics/closedAccessBiocatalysisDrug precursorAsymmetric bioreductionGreen chemistry(s)-(4-chlorophenyl)(phenyl)methanolArticle54710.1016/j.mcat.2023.1134042-s2.0-85166278445Q2WOS:001047298500001Q2