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

Creative Commons License

Özdemir A., Sahin E.

ARABIAN JOURNAL FOR SCIENCE AND ENGINEERING, vol.49, no.6, pp.8225-8235, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 49 Issue: 6
  • Publication Date: 2024
  • Doi Number: 10.1007/s13369-024-08773-5
  • Journal Name: ARABIAN JOURNAL FOR SCIENCE AND ENGINEERING
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aerospace Database, Communication Abstracts, Metadex, Pollution Abstracts, zbMATH, Civil Engineering Abstracts
  • Page Numbers: pp.8225-8235
  • Ondokuz Mayıs University Affiliated: Yes

Abstract

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 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. (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.