A Concise Stereoselective Synthesis of (<i>R</i>)‐2‐Benzylmorpholine and ML398 from (<i>R</i>)‐(−)‐2‐Phenylglycinol

Torres, S.V. Boned; Velasco, Manuel; Gallegos‐Rojas, José Ángel; Bernès, Syl­vain; Orea, María L.; Terán, Joel L.; Huelgas, Gabriela; Gómez-Calvario, Víctor; Juárez, Jorge R.

doi:10.1002/jhet.3657

Cited by 1 publication

(1 citation statement)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As initial synthetic targets, we selected benzyl-substituted analogues of morpholine a and piperidine b due to their prevalence in in APIs such as dopamine receptor antagonists and acetylcholinesterase inhibitors. [22][23][24][25][26][27][28] To identify a suitable candidate for enzyme engineering, we turned to our previously established panel of metagenomic IREDs. [17] In particular, pIR-361 (henceforth named RedAm-361) has previously been shown to tolerate dimethylamine as a substrate.…”

Section: Resultsmentioning

confidence: 99%

Engineered Biocatalysts for Enantioselective Reductive Aminations of Cyclic Secondary Amines

et al. 2023

View full text Add to dashboard Cite

Reductive aminases (RedAms) have recently emerged as promising biocatalysts for the synthesis of chiral secondary amines by coupling primary amines with aldehydes/ketones. However, access to tertiary amines remains more problematic, particularly when coupling ketones with secondary amines. Here we show that the scope of these enzymes can be extended to allow selective reductive aminations of cyclic secondary amines, such as piperidines and morpholines, with both aldehydes and ketones. These biotransformations provide access to important motifs found in active pharmaceutical ingredients and other bioactive molecules. RedAm‐361, discovered from a metagenomic library, was engineered via directed evolution to allow efficient coupling of cyclic amines with carbonyl partners, including dynamic kinetic resolutions of α‐functionalized aldehydes and enantioselective amination of ketones. These RedAms now serve as valuable scaffolds for the engineering of industrial biocatalysts to produce key pharmaceutical intermediates.

show abstract