In this study, an enantioselective d-carbamoylase (AcHyuC) was identified from Arthrobacter crystallopoietes with optimum pH of 8.5, much more compatible with hydantoinase process than other reported d-N-carbamoylases. AcHyuC has a substrate preference for aromatic carbamoyl-compounds. The dynamic kinetic resolution (DKR) cascade was developed by combining this AcHyuC with hydantoin racemase from Arthrobacter aurescens (AaHyuA) and d-hydantoinase from Agrobacterium tumefaciens (AtHyuH) for enantioselective resolution of l-indolylmethylhydantoin into d-Trp. The optimum pH of DKR cascade reaction was determined to be 8.0, and PEG 400 could facilitate the reaction. As much as 80mM l-indolylmethylhydantoin could be fully converted to d-Trp within 12h at 0.5L scale, with 99.4% yield, >99.9% e.e. and productivity of 36.6gLd. This study provides a new d-carbamoylase compatible with the DKR cascade for efficient production of optically pure d-Trp from l-indolylmethylhydantoin.
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http://dx.doi.org/10.1016/j.biortech.2017.09.162 | DOI Listing |
Angew Chem Int Ed Engl
November 2024
Laboratory of Biocatalysis and Biotransformation, Department of Drugs Technology and Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Koszykowa 75, 00-662, Warsaw, Poland.
Dynamic kinetic resolution (DKR) is a key method used to prepare optically pure compounds in 100 % theoretical yield starting from racemic substrates by combining the interconversion of substrate enantiomers with an enantioselective transformation. Various chemoenzymatic DKR approaches have been developed to deracemize secondary alcohols, typically requiring an organic solvent to facilitate enantioselective acylation, primarily catalyzed by lipases, alongside racemization mediated by an achiral, non-enzymatic catalyst. Achieving both steps in an aqueous solution remained elusive.
View Article and Find Full Text PDFChem Commun (Camb)
April 2024
Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710062, China.
Ru-catalyzed asymmetric hydrogenation of α-substituted α,β-unsaturated ketones has been developed for the enantioselective synthesis of chiral α-substituted secondary alcohols with high diastereo- and enantioselectivities (up to >99 : 1 dr, 98% ee). Mechanistic experiments suggest that the reaction proceeds a Ru-catalyzed asymmetric hydrogenation of the CO bond in concert with a base-promoted allylic alcohol isomerization, and the final stereoselectivities were controlled by a DKR process during the asymmetric hydrogenation of the ketone intermediate.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2023
Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, P. R. China.
The catalytic asymmetric synthesis of phosphorus-containing helicenes remains a formidable challenge, presumably due to the lack of rational design of substrates, right choice of reactions together with highly effective catalysis systems. Herein, we disclosed an efficient and practical DKR-involving (dynamic kinetic resolution) cascade strategy toward synthesizing a novel family of phosphorus-installing helicenes by peptide-mimic phosphonium salt (PPS) catalysis. The sequential process of PPS-catalyzed phospha-Michael attack and copper salt-facilitated aromatization led to the formation of unprecedented phosphorus-containing oxa[5]helicene scaffolds.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
August 2022
School of Cancer and Pharmaceutical Sciences, King's College London, 150 Stamford Street, London, SE1 9NH, UK.
Chiral β-hydroxysulfides are an important class of organic compounds which find broad application in organic and pharmaceutical chemistry. Herein we describe the development of novel biocatalytic and chemoenzymatic methods for the enantioselective synthesis of β-hydroxysulfides by exploiting ketoreductase (KRED) enzymes. Four KREDs were discovered from a pool of 384 enzymes identified and isolated through a metagenomic approach.
View Article and Find Full Text PDFJ Am Chem Soc
October 2019
Department of Chemical Science and Engineering, School of Materials and Chemical Technology , Tokyo Institute of Technology, O-okayama 2-12-1-E4-1 , Meguro-ku, Tokyo 152-8552 , Japan.
A straightforward asymmetric construction of chiral fused γ- and δ-lactones containing multiple contiguous stereocenters was successfully developed by either (1) the dynamic kinetic resolution-asymmetric transfer hydrogenation (DKR-ATH) reaction using oxo-tethered Ru(II) complexes followed by -selective lactonization or (2) the tandem DKR-ATH/lactonization in combination with asymmetric hydrogenation catalyzed by Ru-chiral diphosphine complexes. The expedient protocol is applicable to the enantioselective synthesis of natural wine lactone and a biologically active benzo-fused lactone with an unprecedented level of diastereo- and enantioselectivity.
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