Asymmetric Reduction of Cyclic Imines by Imine Reductase Enzymes in Non-Conventional Solvents.
ChemSusChem
; 17(3): e202301243, 2024 Feb 08.
Article
en En
| MEDLINE
| ID: mdl-37751248
ABSTRACT
The first enantioselective reduction of 2-substituted cyclic imines to the corresponding amines (pyrrolidines, piperidines, and azepines) by imine reductases (IREDs) in non-conventional solvents is reported. The best results were obtained in a glycerol/phosphate buffer 1 1 mixture, in which heterocyclic amines were produced with full conversions (>99 %), moderate to good yields (22-84 %) and excellent S-enantioselectivities (up to >99 % ee). Remarkably, the process can be performed at a 100â
mM substrate loading, which, for the model compound, means a concentration of 14.5â
g L-1 . A fed-batch protocol was also developed for a convenient scale-up transformation, and one millimole of substrate 1 a was readily converted into 120â
mg of enantiopure amine (S)-2 a with a remarkable 80 % overall yield. This aspect strongly contributes to making the process potentially attractive for large-scale applications in terms of economic and environmental sustainability for a good number of substrates used to produce enantiopure cyclic amines of high pharmaceutical interest.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oxidorreductasas
/
Iminas
Idioma:
En
Revista:
ChemSusChem
Asunto de la revista:
QUIMICA
/
TOXICOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia