Effective biocatalytic synthesis of enentiopure (R)-1,2-diphenylethanol as a pharmaceutical precursor using whole-cell biocatalyst

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, 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 high-gram 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.