Asymmetric Synthesis of N-Hydroxyethyl Amino Indane Derivatives Catalyzed by an Engineered Imine Reductase

Org Lett. 2025 Apr 18;27(15):4063-4067. doi: 10.1021/acs.orglett.5c01095. Epub 2025 Apr 7.

Abstract

Asymmetric synthesis of chiral N-hydroxyethyl amino indane derivatives remains challenging. In this study, an imine reductase mutant (IR262-F185E/F229L) was identified with high enantioselectivity toward various N-hydroxyethyl imino derivatives. Furthermore, a continuous fed-batch strategy was designed to avoid the hydrolysis of imines, and up to 200 mM 1-((2-hydroxyethyl)imino)-2,3-dihydro-1H-indene-4-carbonitrile could be completely converted into (S)-1-((2-hydroxyethyl)amino)-2,3-dihydro-1H-indene-4-carbonitrile in 70% isolated yield and >99% ee, demonstrating a great potential for the synthesis of the ozanimod intermediate in industrial applications.

MeSH terms

  • Catalysis
  • Imines* / chemistry
  • Imines* / metabolism
  • Indans* / chemical synthesis
  • Indans* / chemistry
  • Molecular Structure
  • Oxidoreductases* / chemistry
  • Oxidoreductases* / genetics
  • Oxidoreductases* / metabolism
  • Stereoisomerism

Substances

  • Oxidoreductases
  • Imines
  • Indans