4.5 Article

Transaminase-mediated chiral selective synthesis of (1R)-(3-methylphenyl)ethan-1-amine from 1-(3-methylphenyl)ethan-1-one: process minutiae, optimization, characterization and 'What If studies'

Journal

BIOPROCESS AND BIOSYSTEMS ENGINEERING
Volume 46, Issue 2, Pages 207-225

Publisher

SPRINGER
DOI: 10.1007/s00449-022-02824-7

Keywords

Transaminases (ATA-025); Transamination; 1-(3-methylphenyl)ethan-1-one; (1R)-(3-methylphenyl)ethan-1-amine; Chiral selective synthesis; Process optimization and development

Ask authors/readers for more resources

This study screened transaminases capable of carrying out chiral selective transamination of 1-(3-methylphenyl)ethan-1-one to (1R)-(3-methylphenyl)ethan-1-amine and found that ATA-025 was the best enzyme and dimethylsulfoxide was the best co-solvent. By optimizing variables such as enzyme loading, substrate loading, temperature, and pH, the study achieved maximum conversion, good product formation, and higher yield. The green and novel enzymatic approach using the optimized process can be used for the synthesis of different active pharma entities.
Transaminases capable of carrying out chiral selective transamination of 1-(3-methylphenyl)ethan-1-one to (1R)-(3-methylphenyl)ethan-1-amine were screened, and ATA-025 was the best enzyme, while dimethylsulfoxide (10% V/V) was the best co-solvent for said bioconversion. The variables such as enzyme loading, substrate loading, temperature, and pH for development of process displaying maximum conversion with good product formation and higher yield were optimized. The ambient processing conditions were 10% enzyme loading/50 g/L substrate loading/45 & DEG;C/pH 8.0, and 5% enzyme loading/36.78 g/L substrate loading/42.66 & DEG;C/pH 8.2 displaying maximum conversion 99.01 & PLUSMN; 2.47% and 96.115 & PLUSMN; 1.97%, and 76.93 & PLUSMN; 1.05% and 73.12 & PLUSMN; 1.04% yield with one factor at a time approach and numerical optimization with Box Behnken Design, respectively. In the final optimized reaction, ATA-025 showed the highest 99.22 & PLUSMN; 2.61% conversion, 49.55 g/L product formation, with an actual product recovery of 38.16 g corresponding to a product yield 77.03 & PLUSMN; 1.01% with respect to the product formed after reaction. The purity of recovered product (1R)-(3-methylphenyl)ethan-1-amine formed was & GE; 99% (RP-HPLC), and chiral purity & GE; 98.5% (Chiral-GC), and it was also confirmed and characterized with instrumental methods using boiling point, LC-MS, ATR-FTIR, and H-1 NMR. The findings of 'What If' studies performed by investigating timely progress of reaction on gram scale by drastically changing the process parameters revealed a substantial modification in process variables to achieve desired results. (1R)-(3-methylphenyl)ethan-1-amine synthesized by green, facile and novel enzymatic approach with an optimized process could be used for synthesis of different active pharma entities.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available