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author:

Wang, Zexu (Wang, Zexu.) [1] | Wu, Xiaofan (Wu, Xiaofan.) [2] | Li, Zhining (Li, Zhining.) [3] | Huang, Zedu (Huang, Zedu.) [4] | Chen, Fener (Chen, Fener.) [5]

Indexed by:

EI

Abstract:

We report here the stereoselective bioreduction of α-nitro ketones catalyzed by ketoreductases (KREDs) with publicly known sequences. YGL039w and RasADH/SyADH were able to reduce 23 class I substrates (1-aryl-2-nitro-1-ethanone (1)) and ten class II substrates (1-aryloxy-3-nitro-2-propanone (4)) to furnish both enantiomers of the corresponding β-nitro alcohols, with good-to-excellent conversions (up to >99%) and enantioselectivities (up to >99% ee) being achieved in most cases. To the best of our knowledge, KRED-mediated reduction of class II α-nitro ketones (1-aryloxy-3-nitro-2-propanone (4)) is unprecedented. Select β-nitro alcohols, including the synthetic intermediates of bioactive molecules (R)-tembamide, (S)-tembamide, (S)-moprolol, (S)-toliprolol and (S)-propanolol, were stereoselectively synthesized in preparative scale with 42% to 90% isolated yields, showcasing the practical potential of our developed system in organic synthesis. Finally, the advantage of using KREDs with known sequence was demonstrated by whole-cell catalysis, in which β-nitro alcohol (R)-2k, the key synthetic intermediate of hypoglycemic natural product (R)-tembamide, was produced in a space-time yield of 178 g L−1 d−1 as well as 95% ee by employing the whole cells of a recombinant E. coli strain coexpressing RasADH and glucose dehydrogenase as the biocatalyst. © The Royal Society of Chemistry.

Keyword:

Catalysis Escherichia coli Ketones Stereoselectivity Synthesis (chemical)

Community:

  • [ 1 ] [Wang, Zexu]Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, 220 Handan Road, Shanghai; 200433, China
  • [ 2 ] [Wang, Zexu]Shanghai Engineering Research Center of Industrial Asymmetric Catalysis of Chiral Drugs, 220 Handan Road, Shanghai; 200433, China
  • [ 3 ] [Wu, Xiaofan]College of Chemical Engineering, Fuzhou University, 2 Xueyuan Road, Fuzhou; 350100, China
  • [ 4 ] [Li, Zhining]Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, 220 Handan Road, Shanghai; 200433, China
  • [ 5 ] [Li, Zhining]Shanghai Engineering Research Center of Industrial Asymmetric Catalysis of Chiral Drugs, 220 Handan Road, Shanghai; 200433, China
  • [ 6 ] [Huang, Zedu]Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, 220 Handan Road, Shanghai; 200433, China
  • [ 7 ] [Huang, Zedu]Shanghai Engineering Research Center of Industrial Asymmetric Catalysis of Chiral Drugs, 220 Handan Road, Shanghai; 200433, China
  • [ 8 ] [Chen, Fener]Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, 220 Handan Road, Shanghai; 200433, China
  • [ 9 ] [Chen, Fener]Shanghai Engineering Research Center of Industrial Asymmetric Catalysis of Chiral Drugs, 220 Handan Road, Shanghai; 200433, China

Reprint 's Address:

  • [huang, zedu]engineering center of catalysis and synthesis for chiral molecules, department of chemistry, fudan university, 220 handan road, shanghai; 200433, china;;[huang, zedu]shanghai engineering research center of industrial asymmetric catalysis of chiral drugs, 220 handan road, shanghai; 200433, china

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Source :

Organic and Biomolecular Chemistry

ISSN: 1477-0520

Year: 2019

Issue: 14

Volume: 17

Page: 3575-3580

3 . 4 1 2

JCR@2019

2 . 9 0 0

JCR@2023

ESI HC Threshold:184

JCR Journal Grade:1

CAS Journal Grade:3

Cited Count:

WoS CC Cited Count:

SCOPUS Cited Count:

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 4

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