Publications by authors named "Nan-Wei Wan"

12 Publications

  • Page 1 of 1

Regiodivergent and stereoselective hydroxyazidation of alkenes by biocatalytic cascades.

iScience 2021 Aug 17;24(8):102883. Epub 2021 Jul 17.

Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, China.

Asymmetric functionalization of alkenes allows the direct synthesis of a wide range of chiral compounds. Vicinal hydroxyazidation of alkenes provides a desirable path to 1,2-azidoalcohols; however, existing methods are limited by the control of stereoselectivity and regioselectivity. Herein, we describe a dual-enzyme cascade strategy for regiodivergent and stereoselective hydroxyazidation of alkenes, affording various enantiomerically pure 1,2-azidoalcohols. The biocatalytic cascade process is designed by combining styrene monooxygenase-catalyzed asymmetric epoxidation of alkenes and halohydrin dehalogenase-catalyzed regioselective ring opening of epoxides with azide. Additionally, a one-pot chemo-enzymatic route to chiral -hydroxytriazoles from alkenes is developed via combining the biocatalytic cascades and Cu-catalyzed azide-alkyne cycloaddition.
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http://dx.doi.org/10.1016/j.isci.2021.102883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353479PMC
August 2021

Palladium-catalyzed asymmetric allylic alkylation of 3-aminooxindoles to access chiral homoallylic aminooxindoles.

Org Biomol Chem 2021 Jun;19(21):4720-4725

Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi 563000, China. and Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China.

An organometal catalytic conversion of 3-aminooxindoles for the diastereo- and enantioselective synthesis of homoallylic aminooxindoles has been described. The asymmetric allylic alkylation of 3-aminooxindoles with allyl carboxylates proceeded smoothly to afford a series of chiral 3-allyl-3-aminooxindoles. This work offers an alternative route to build these scaffolds. The application of this protocol is also highlighted by a significant conversion of products to the potential applicable spiro[indoline-3,2'-pyrrolidin]-2-one derivatives.
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http://dx.doi.org/10.1039/d1ob00550bDOI Listing
June 2021

Synthesis of chromone-containing polycyclic compounds via palladium-catalyzed [2 + 2 + 1] annulation.

Org Biomol Chem 2020 02 27;18(6):1112-1116. Epub 2020 Jan 27.

Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi 563006, P. R. China. and Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, P. R. China.

A palladium-catalyzed [2 + 2 + 1] domino annulation of 3-iodochromones, α-bromo carbonyl compounds, and tetracyclododecene (TCD) is described. This approach provides a facile, efficient and atom-economical route to a variety of chromone-containing polycyclic compounds bearing fused/bridged-ring systems in good yields (up to 81%) with excellent diastereoselectivities (99 : 1 dr in all cases).
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http://dx.doi.org/10.1039/c9ob02690hDOI Listing
February 2020

Generation of Difluorodiazoethane (CFHCHN): Application in the Regioselective Synthesis of CFH-Containing Pyrazoles.

Org Lett 2019 11 23;21(21):8751-8755. Epub 2019 Oct 23.

Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, School of Pharmacy , Zunyi Medical University , Zunyi 563006 , P. R. China.

A new method for the generation of difluorodiazoethane (CFHCHN) and a procedure for its efficient use in [3 + 2] cycloaddition with nitroolefins by the AcOH/O catalyst system were developed by using a simple two-chamber system. The method provides a facile and straightforward access to a series of 4-substituted 5-difluoromethyl-3-nitro-1-pyrazoles that are of interest in medicinal chemistry. Interestingly, the key factor for the success of this method is the efficient preparation of CFHCHN by an process.
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http://dx.doi.org/10.1021/acs.orglett.9b03371DOI Listing
November 2019

2,2-Bifunctionalization of Norbornene in Palladium-Catalyzed Domino Annulation.

Org Lett 2019 11 22;21(21):8857-8860. Epub 2019 Oct 22.

Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, School of Pharmacy , Zunyi Medical University , Zunyi 563006 , PR China.

A palladium-catalyzed three-component [2 + 3 + 1] domino annulation among 3-iodochromones, α-bromoacetophenones, and norbornene is presented, affording various chromone-containing polycyclic compounds bearing fused/spiro/bridged-ring systems. For the first time, the 2,2-bifunctionalization of norbornene was realized in palladium-catalyzed domino reaction. This cyclization characterizes three new bonds (two C-C and one C-O) in a single operation and produces nontrivial spiro-norbornane fragments in comparison with a traditional palladium-catalyzed process involving norbornene.
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http://dx.doi.org/10.1021/acs.orglett.9b03565DOI Listing
November 2019

Asymmetric [3 + 2] Cycloaddition Reaction of Isatin-Derived MBH Carbonates with 3-Methyleneoxindoles: Enantioselective Synthesis of 3,3'-Cyclopentenyldispirooxindoles Incorporating Two Adjacent Quaternary Spirostereocenters.

J Org Chem 2018 09 11;83(17):10465-10475. Epub 2018 Jul 11.

Generic Drug Research Center of Guizhou Province, School of Pharmacy , Zunyi Medial University , Zunyi 563000 , China.

A highly regio- and stereoselective [3 + 2] cycloaddition reaction for constructing novel 3,3'-cyclopentenyldispirooxindoles incorporating two adjacent quaternary spirostereocenters is reported. Under the mild conditions, the asymmetric annulation of isatin-derived MBH carbonates with 3-methyleneoxindoles involving a chiral tertiary amine catalyst provides the corresponding dispirooxindole frameworks with an extraordinary level of enantioselective control. Further synthetic utility of this method was demonstrated by the gram-scale experiment and simple transformation of the obtained product. Moreover, a plausible mechanism for this annulation reaction was also proposed on the basis of the control experiments.
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http://dx.doi.org/10.1021/acs.joc.8b01506DOI Listing
September 2018

A Protocol for the Synthesis of CFH-Containing Pyrazolo[1,5- c]quinazolines from 3-Ylideneoxindoles and in Situ Generated CFHCHN.

J Org Chem 2018 06 4;83(12):6556-6565. Epub 2018 Jun 4.

Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy , Zunyi Medical University , Zunyi 563000 , China.

Herein is disclosed a selective and facile approach for the construction of CFH-containing pyrazolo[1,5- c]quinazolines from easily accessible 3-ylideneoxindoles and in situ generated CFHCHN. The reaction involving a [3 + 2] cycloaddition/1,3-H shift/rearrangement/dehydrogenation cascade proceeded smoothly at room temperature in the absence of catalyst and additive. Moreover, this metal-free process along with mild conditions is desirable and valuable for the pharmaceutical industry. Importantly, this reaction features a broad substrate scope, good functional group tolerance, and gram-scale synthesis.
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http://dx.doi.org/10.1021/acs.joc.8b00866DOI Listing
June 2018

Diastereoselective [3 + 2] cycloaddition of 3-ylideneoxindoles with in situ generated CFHCHN: syntheses of CFH-containing spirooxindoles.

Org Biomol Chem 2017 Jul;15(26):5571-5578

Generic Drug Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, China.

An efficient [3 + 2] cycloaddition of 3-ylideneoxindoles with in situ generated CFHCHN for the syntheses of spirooxindoles has been developed. This methodology gives access to a range of relatively complex spirooxindoles featuring a CFH group and three contiguous stereogenic centers in up to 84% yield and 99 : 1 trans/cis.
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http://dx.doi.org/10.1039/c7ob01266gDOI Listing
July 2017

An enzymatic method for determination of azide and cyanide in aqueous phase.

J Biotechnol 2015 Nov 7;214:27-32. Epub 2015 Sep 7.

Institute of Bioengineering, Zhejiang University of Technology, Hangzhou 310014, PR China; Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology, Hangzhou 310014, PR China. Electronic address:

A halohydrin dehalogenase (HHDH-PL) from Parvibaculum lavamentivorans DS-1 was characterized and applied to determine azide and cyanide in the water. In this methodology, HHDH-PL catalysed azide and cyanide to react with butylene oxide and form corresponding β-substituted alcohols 1-azidobutan-2-ol (ABO) and 3-hydroxypentanenitrile (HPN) that could be quantitatively detected by gas chromatograph. The detection calibration curves for azide (R(2)=0.997) and cyanide (R(2)=0.995) were linear and the lower limits of detection for azide and cyanide were 0.1 and 0.3mM, respectively. Several other nucleophiles were identified having no effect on the analysis of azide and cyanide, excepting nitrite which influenced the detection of cyanide. This was the first report of a biological method to determine the inorganic azide and cyanide by converting them to the measurable organics.
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http://dx.doi.org/10.1016/j.jbiotec.2015.09.001DOI Listing
November 2015

An efficient high-throughput screening assay for rapid directed evolution of halohydrin dehalogenase for preparation of β-substituted alcohols.

Appl Microbiol Biotechnol 2015 May 25;99(9):4019-29. Epub 2015 Mar 25.

Institute of Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China.

Halohydrin dehalogenases (HHDHs) are an important class of enzymes for preparing optically active haloalcohols, epoxides, and β-substituted alcohols. However, natural HHDHs rarely meet the requirements of industrial applications. Here, a novel high-throughput screening (HTS) methodology for directed evolution of HHDH was developed based on the colorimetric determination of azide. In this method, azide was involved in the HHDH-catalyzed ring-opening process and the decrease of azide was used to quantitatively evaluate HHDH activity. The HTS methodology was simple and sensitive (ε460 = 1.2173 × 10(4) L mol(-1) cm(-1)) and could be performed in a microplate format using whole cells. To verify the efficiency of the HTS methodology, it was adopted to engineer a HHDH (HHDH-PL) from Parvibaculum lavamentivorans DS-1, which was applied in the process for ethyl (R)-4-cyano-3-hydroxybutanoate (HN) by the conversion of ethyl (S)-4-chloro-3-hydroxybutanoate ((S)-CHBE)). A random mutant library containing 2500 colonies was screened using the HTS methodology, and three beneficial mutants F176M, A187R, and A187S were obtained. By combining the beneficial mutated residues, the variant F176M/A187R was identified with 2.8-fold higher catalytic efficiency for preparation of HN. The high-throughput colorimetric assay would be very useful for directed evolution of HHDH for preparing β-substituted alcohols.
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http://dx.doi.org/10.1007/s00253-015-6527-zDOI Listing
May 2015

Purification, gene cloning, and characterization of a novel halohydrin dehalogenase from Agromyces mediolanus ZJB120203.

Appl Biochem Biotechnol 2014 Sep 29;174(1):352-64. Epub 2014 Jul 29.

Institute of Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China.

A novel halohydrin dehalogenase (HHDH), catalyzing the transformation of 1,3-dichloro-2-propanol (1,3-DCP) to epichlorohydrin (ECH), was purified from Agromyces mediolanus ZJB120203. The molecular mass of the enzyme was estimated to be 28 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). A 735-bp nucleotide fragment was obtained based on the N-terminal and internal amino acid sequences of the purified HHDH. The gene codes a protein sequence with 244 amino acid residues, and the protein sequence shows high similarity to Hhe AAD2 (HHDH from Arthrobacter sp. AD2), defined as Hhe AAm, which is the seventh reported HHDH. Expression of Hhe AAm was carried out in Escherichia coli and purification was performed by nickel-affinity chromatography. The recombinant HheAAm possessed an optimal pH of 8.5 and an optimal temperature of 50 °C and manifested a K m of 4.58 mM and a V max of 3.84 μmol/min(/)mg. The activity of Hhe AAm was not significantly affected by metal ions such as Zn(2+), Ca(2+), Cu(2+), and EDTA, but was strongly inhibited by Hg(2+) and Ag(+). In particular, the Hhe AAm exhibits an enantioselectivity for the conversion of prochiral 1,3-DCP to (S)-ECH. The applications of the Hhe AAm as a catalyst for asymmetric synthesis are promising.
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http://dx.doi.org/10.1007/s12010-014-1111-zDOI Listing
September 2014

Enzymatic production of 5'-inosinic acid by a newly synthesised acid phosphatase/phosphotransferase.

Food Chem 2012 Sep 8;134(2):948-56. Epub 2012 Mar 8.

Institute of Bioengineering, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China.

5'-Nucleotides including 5'-inosinic acid have characteristic taste and important application in various foods as flavour potentiators. The selective nucleoside acid phosphatase/phosphotransferase (AP/PTase) can catalyse the synthesis of 5'-nucleotides by transfer of phosphate groups. In this study, a 747-bp gene encoding AP/PTase from Escherichia blattae was synthesised. After expression, the recombinant AP/PTase was purified using nickel-NTA. The optimal temperature and pH of this enzyme were 30°C and 5.0, respectively. The activity was partially inhibited by metal ions such as Hg(2+), Ag(+) and Cu(2+), but not by chelating reagents such as EDTA. The values of K(m) and V(max) for inosine were 40 mM and 3.5 U/mg, respectively. Using this purified enzyme, 16.83 mM of 5'-IMP was synthesised from 37 mM of inosine and the molar yield reached 45.5%. Homology modelling and docking simulation were discussed.
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http://dx.doi.org/10.1016/j.foodchem.2012.02.213DOI Listing
September 2012
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