Enantioselective reduction of sulfur-containing cyclic imines through biocatalysis

Nature Communications
Nadine ZumbrägelHarald Gröger

Abstract

The 3-thiazolidine ring represents an important structural motif in life sciences molecules. However, up to now reduction of 3-thiazolines as an attractive approach failed by means of nearly all chemical reduction technologies for imines. Thus, the development of an efficient general and enantioselective synthetic technology giving access to a range of such heterocycles remained a challenge. Here we present a method enabling the reduction of 3-thiazolines with high conversion and high to excellent enantioselectivity (at least 96% and up to 99% enantiomeric excess). This technology is based on the use of imine reductases as catalysts, has a broad substrate range, and is also applied successfully to other sulfur-containing heterocyclic imines such as 2H-1,4-benzothiazines. Moreover the effiency of this biocatalytic technology platform is demonstrated in an initial process development leading to 99% conversion and 99% enantiomeric excess at a substrate loading of 18 g/L in the presence of designer cells.

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Citations

Nov 11, 2019·Emerging Topics in Life Sciences·David Tew
Sep 18, 2020·Chembiochem : a European Journal of Chemical Biology·Peter StockingerBettina M Nestl
Mar 27, 2021·ChemMedChem·Nefeli GribouraConstantinos G Neochoritis
Dec 19, 2018·The Journal of Organic Chemistry·Nadine ZumbrägelHarald Gröger
May 3, 2019·The Journal of Organic Chemistry·Christian MertenNora M Kreienborg
Aug 24, 2019·Journal of the American Chemical Society·Travis LundriganAlexander W H Speed

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Methods Mentioned

BETA
circular dichroism
NMR

Software Mentioned

Gaussian
Spartan
MMFF

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