Asymmetric Synthesis of <i>N</i>-Hydroxyethyl Amino Indane Derivatives Catalyzed by an Engineered Imine Reductase
Asymmetric synthesis of chiral <i>N</i>-hydroxyethyl amino indane derivatives remains challenging. In this study, an imine reductase mutant (IR262-F185E/F229L) was identified with high enantioselectivity toward various <i>N</i>-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-1<i>H</i>-indene-4-carbonitrile could be completely converted into (<i>S</i>)-1-((2-hydroxyethyl)amino)-2,3-dihydro-1<i>H</i>-indene-4-carbonitrile in 70% isolated yield and >99% ee, demonstrating a great potential for the synthesis of the ozanimod intermediate in industrial applications.
Authors
- Dunming Zhu (ORCID: https://orcid.org/0000-0001-8783-5358)
- Jinhui Feng (ORCID: https://orcid.org/0000-0001-9320-7323)
- Shuhong Mao (ORCID: https://orcid.org/0000-0003-2090-0367)
- Zefei Xu (ORCID: https://orcid.org/0000-0002-3710-3623)
- Qiaqing Wu (ORCID: https://orcid.org/0000-0001-7405-1562)
- Peiyuan Yao (ORCID: https://orcid.org/0000-0003-4029-5985)
- Jinyang Li (ORCID: https://orcid.org/0000-0001-8344-6494)
Institutions
- Tianjin University of Science and Technology (CN)
- Chinese Academy of Sciences (CN)
- Tianjin Institute of Industrial Biotechnology (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-04-07
- DOI
- https://doi.org/10.1021/acs.orglett.5c01095
- Citations
- 2
- Primary Topic
- Enzyme Catalysis and Immobilization
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- National Key Research and Development Program of China