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    Effective biocatalytic synthesis of enentiopure ( R )-1,2-diphenylethanol as a pharmaceutical precursor using whole-cell biocatalyst
    (Elsevier, 2024) Cakmak, Fadile; Ozdemir, Akin; Dertli, Enes; Sahin, Engin
    Optically active alcohols are crucial precursors. 1,2-Diarylethanols and their analogues constitute a significant group of substances of biological significance. The biocatalytic synthesis of ( R )-1,2-diphenylethanol ( ( R )-2 ), which can be utilized as a precursor to important drugs, is still not at the desired level in terms of substrate amount and production process. This study asymmetrically reduced 1,2-diphenylethanone (1) using the Lactobacillus paracasei BD87E6 biocatalyst and a novel orthogonal quadratic design -embedded optimization approach. The following reaction optimization conditions were determined using the suggested optimization technique: pH = 6, temperature = 31 C-degrees , incubation period = 48 h, and agitation speed=134 rpm. In addition, the reaction conversion was estimated to be 99.38 %, and the product 's enantiomeric excess (ee) was estimated to be 99.12 %. Further, ( R )-2 was produced with >99 % ee, >99 % conversion, and 98 % yield in the experimental investigation under the established optimum conditions. This study is the first attempt to reduce substrate 1 to (R) or (S)-2 using a mathematical optimization method in the presence of a biocatalyst. Furthermore, on a highgram scale, 1 (15.70 g) was entirely transformed into ( R )-2 (15.54 g, 98 % isolated yield). Notably, this study is also the first to perform the gram -scale production of ( R )-2 using a novel optimization approach and a biocatalyst. Finally, the innovative and novel orthogonal quadratic design -embedded optimization technique has been demonstrated as an efficient, cost-effective, and environmentally friendly biocatalytic procedure for synthesizing ( R )-2 .