A Multi-response Nonlinear Programming Model with an Inscribed Design to Optimize Bioreduction Conditions of (S)-phenyl (pyridin-2-yl)methanol by Leuconostoc pseudomesenteroides N13

• Published in: Arabian journal for science and engineering (2011) 2024, Vol.49 (6), p.8225-8235
• Main Authors: Özdemir, Akın, Şahin, Engin
• Format: Article
• Language: English
• Subjects: Analgesics; Asymmetry; Bacteria; Biocatalysts; Chemical synthesis; Design optimization; Engineering; Humanities and Social Sciences; Methanol; multidisciplinary; Nonlinear programming; Nonlinear response; Optimization; Optimization models; Production methods; Research Article-Chemical Engineering; Science; Substrates
• ISSN: 2193-567X; 1319-8025; 2191-4281
• DOI: 10.1007/s13369-024-08773-5

Asymmetric bioreductions have the potential to synthesize chiral alcohols when catalyzed by biocatalysts. Nevertheless, the ( S )-phenyl (pyridin-2-yl)methanol ( ( S )-2 ) 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 ( 1 ) 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 °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. ( S )-2 was obtained with 99% ee, 99% conversion, and 98% yield while performing a validation experiment using the determined optimized conditions. In addition, 1 with the amount of 11.9 g was converted entirely to ( S )-2 (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 ( S )-2 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 ( S )-2 , which is a green, cost-effective method of producing chiral aryl heteroaryl methanol.