Asymmetric Synthesis of N-Hydroxyethyl Amino Indane Derivatives Catalyzed by an Engineered Imine Reductase DOI
Jinyang Li, Zefei Xu, Jinhui Feng

и другие.

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

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 imino derivatives. Furthermore, a continuous fed-batch strategy designed to avoid the hydrolysis imines, and up 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 >99% ee, demonstrating great potential for ozanimod intermediate industrial applications.

Язык: Английский

Mutagenesis of a Single Site Inverts the Stereopreference of Imine Reductase DOI
Yitong Li,

Yunyun Yang,

Mengting Zhang

и другие.

ACS Catalysis, Год журнала: 2025, Номер 15(3), С. 2192 - 2199

Опубликована: Янв. 23, 2025

Development of a generally applicable means to invert the stereoselectivity an enzymatic reaction is paramount significance. Through protein structure-guided mutagenesis, Met235 was identified as crucial residue influencing imine reductase AtIRED-catalyzed reduction sterically demanding 1-substituted dihydro-β-carbolines (DHβCs), particularly with single mutants M235A/C/G/I/S/T/V displaying simultaneously inverted and improved catalytic activity relative wild-type (WT) enzyme. Using best variant M235A biocatalyst, five tetrahydro-β-carbolines (THβCs) (R)-configuration were afforded in 48–81% isolated yields 89 → 99% ee. Combined our previous synthesis (S)-stereoisomer using WT other variants, we have established stereocomplementary access these THβCs. Based on solved crystal structure complexed NADP+ substrate 1-t-butyl-DHβC, mutation-induced relief undesired steric clashes rationalized main cause observed inversion enhancement. This influence stereopreference exerted by mutation transferred successfully Y-type IREDs and, part, D-type IREDs, representing first demonstration this kind knowledge transfer between reductases. The current study identifies stereocontrol element it offers potentially generic strategy switch fascinating enzymes.

Язык: Английский

Процитировано

0
Reductive amination: Methods for cell-free and whole-cell biocatalysis DOI
Vasilis Tseliou, Matteo Damian,

Josemarco Mendoza-Avila

и другие.

Methods in enzymology on CD-ROM/Methods in enzymology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Structure-guided mining of stereoselective reductive aminases for biocatalytic stereodivergent synthesis of chiral piperidinamine and derivatives DOI
Wen Zhang,

Xiangyu Zheng,

Yudong Hu

и другие.

Journal of Biotechnology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Asymmetric Synthesis of N-Hydroxyethyl Amino Indane Derivatives Catalyzed by an Engineered Imine Reductase DOI
Jinyang Li, Zefei Xu, Jinhui Feng

и другие.

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

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 imino derivatives. Furthermore, a continuous fed-batch strategy designed to avoid the hydrolysis imines, and up 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 >99% ee, demonstrating great potential for ozanimod intermediate industrial applications.

Язык: Английский

Процитировано

0