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. 2022 Jul 8;9(1):73.
doi: 10.1186/s40643-022-00560-0.

Coupling metal and whole-cell catalysis to synthesize chiral alcohols

Hang Yin #  1   2 , Peng-Qian Luan #  2 , Yu-Fei Cao  3 , Jun Ge  4   5   6 , Wen-Yong Lou  7
Affiliations

Coupling metal and whole-cell catalysis to synthesize chiral alcohols

Hang Yin et al. Bioresour Bioprocess. .

Abstract

Background: The combination of metal-catalyzed reactions and enzyme catalysis has been an essential tool for synthesizing chiral pharmaceutical intermediates in the field of drug synthesis. Metal catalysis commonly enables the highly efficient synthesis of molecular scaffolds under harsh organic conditions, whereas enzymes usually catalyze reactions in mild aqueous medium to obtain high selectivity. Since the incompatibility between metal and enzyme catalysis, there are limitations on the compatibility of reaction conditions that must be overcome.

Findings: We report a chemoenzymatic cascade reaction involved Palladium (Pd) catalyzed Suzuki-Miyaura coupling and whole-cell catalyzed C = O asymmetric reduction for enantioselective synthesis of value-added chiral alcohol. The cell membrane serves as a natural barrier can protect intracellular enzymes from organic solvents.

Conclusions: With dual advantages of cascade catalysis and biocompatibility, our work provides a rational strategy to harvest chiral alcohols in high yield and excellent enantioselectivity, as a channel to establish chemoenzymatic catalysis.

Keywords: (S)-4-chlorobenzhydrol; Chemoenzymatic cascade catalysis; Chiral alcohol; Metal catalysis; Whole-cell catalysis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Scheme 1
Scheme 1
Schematic diagram of one pot chemoenzymatic process for (S)-4-chlorobenzhydrol
Fig. 1
Fig. 1
Optimization studies of Pd catalysis. (a) Ratio of substrates (a: 4-chlorobenzoyl chloride; b: phenylboronic acid); (b) loading of bases; (c) loading of catalysts; (d) reaction time and different concentrations of substrates of 4-chlorobenzoyl chloride
Fig. 2
Fig. 2
Comparison of different strains and optimization concentrations of E. coli (KmCR). (a) Strains; (b) pH; (c) reaction temperature; (d) reaction time
Fig. 3
Fig. 3
Chemo-enzymatic cascade catalysis. (a) Yield of ketone in the organic–aqueous system; (b) yield of alcohol at the one-pot sequential process; (c) sequential reaction diagram; (d) yield of alcohol at different concentrations of substrates (4-chlorobenzoyl chloride)
See this image and copyright information in PMC

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