A Multi-Response Nonlinear Programming Model With an Inscribed Design to Optimize Bioreduction Conditions of (S)-Phenyl (Pyridin-2 by Leuconostoc Pseudomesenteroides N13

Abstract

Asymmetric bioreductions have the potential to synthesize chiral alcohols when catalyzed by biocatalysts. Nevertheless, the (S)-phenyl (pyridin-2-yl)methanol (<bold>(</bold><bold>S</bold><bold>)-2</bold>) analgesic synthesis poses significant challenges concerning unsatisfactory substrate amount and production method. Thus, this study proposes an inscribed design-focused multi-response nonlinear optimization model for the asymmetric reduction of the phenyl(pyridin-2-yl)methanone (<bold>1</bold>) with Leuconostoc pseudomesenteroides N13 biocatalyst. From the novel inscribed design-focused multi-response nonlinear optimization model, optimization conditions of the reaction, such as pH = 6, temperature = 29 degrees C, incubation time = 53 h, and agitation speed = 153 rpm, were found. Also, the reaction conversion was predicted to be 99%, and the product of the enantiomeric excess (ee) was 98.4% under the obtained optimization conditions. <bold>(</bold><bold>S</bold><bold>)-2</bold> was obtained with 99% ee, 99% conversion, and 98% yield while performing a validation experiment using the determined optimized conditions. In addition, <bold>1</bold> with the amount of 11.9 g was converted entirely to <bold>(</bold><bold>S</bold><bold>)-2</bold> (11.79 g, 98% isolated yield) on a high gram scale. Also, this study is noted as the first example of the gram-scale production of <bold>(</bold><bold>S</bold><bold>)-2</bold> using an optimization strategy and biocatalyst. Further, the applicability of the inscribed design-focused optimization model in biocatalytic reactions has been demonstrated and provides an effective process for the analgesic synthesis of <bold>(</bold><bold>S</bold><bold>)-2</bold>, which is a green, cost-effective method of producing chiral aryl heteroaryl methanol.