Publications by authors named "Wen-Bo Liu"

79 Publications

Precatalyst-Enabled Selectivity: Enantioselective NiH-catalyzed anti-Hydrometalative Cyclization of Alkynones to endo- and Hetero-cyclic Allylic Alcohols.

Angew Chem Int Ed Engl 2021 Sep 9. Epub 2021 Sep 9.

Wuhan University, College of Chemistry and Molecular Sciences, 299 BAYI road, WuChang,, 430072, Wuhan, CHINA.

A highly enantioselective NiH-catalyzed hydrocyclization of alkynones with unparalleled anti- and endocyclic selectivities is described. The choice of the precatalysts has significant influence in tuning the regio- and enantio-selectivity. Using Ni(OTs) 2 /Phox as a precatalyst and (EtO) 2 MeSiH as a hydride source, an array of enantioenriched O-, N-, and S-containing heterocyclic tertiary allylic alcohols are obtained in 24-81% yields with 80:20-99:1 er. Mechanistic investigations and synthetic application are also carried out. This study represents an efficient access to a set of allylic alcohols that are unable to access by the state-of-the-art coupling reactions.
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http://dx.doi.org/10.1002/anie.202110815DOI Listing
September 2021

Discovery of 1,2,4-triazine dithiocarbamate derivatives as NEDDylation agonists to inhibit gastric cancers.

Eur J Med Chem 2021 Aug 26;225:113801. Epub 2021 Aug 26.

State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, Jiangsu, People's Republic of China; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, People's Republic of China; Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou, 450001, People's Republic of China. Electronic address:

NEDDylation process regulates multiple physiological functions and signaling pathways, which are still in an equilibrium that favors the survival and proliferation of tumor cells. Unlike inhibitors, NEDDylation agonists are rarely studied. In this work, novel 1,2,4-triazine-dithiocarbamate derivatives were synthesized and evaluated for antiproliferative activity against MGC-803, PC-3 and EC-109 cells. Among them, compound K3 displayed the most potent activity MGC-803, PC-3 and EC-109 cells with IC values of 2.35, 5.71 and 10.1 μM, respectively, which were more potent than 5-FU. Further cellular mechanisms suggested that compound K3 inhibited the cell viability, induced proliferation inhibition, arrested cell cycle at G2/M phase and induced cell apoptosis in MGC-803 and HGC-27 cells. Importantly, compound K3 could interact with NAE1 to promote the NEDDylation of MGC-803 and HGC-27 cells. The promotion of NEDDylation resulted in the degradation of c-IAP and YAP/TAZ, which leads to the induction of cell apoptosis and inhibition of proliferation in MGC-803 and HGC-27 cells. Therefore, as a NEDDylation agonist, compound K3 could effectively inhibit gastric cancer cells. Here, we reported NEDDylation promotion induced by compound K3, which could inhibit the cancer cell lines MGC-803 and HGC-27 and induce the cancer cell apoptosis via prompting the degradation of c-IAP and YAP/TAZ.
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http://dx.doi.org/10.1016/j.ejmech.2021.113801DOI Listing
August 2021

Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone Derivatives.

Molecules 2021 Aug 13;26(16). Epub 2021 Aug 13.

School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.

The chalcone and quinoline scaffolds are frequently utilized to design novel anticancer agents. As the continuation of our work on effective anticancer agents, we assumed that linking chalcone fragment to the quinoline scaffold through the principle of molecular hybridization strategy could produce novel compounds with potential anticancer activity. Therefore, quinoline-chalcone derivatives were designed and synthesized, and we explored their antiproliferative activity against MGC-803, HCT-116, and MCF-7 cells. Among these compounds, compound exhibited a most excellent inhibitory potency against MGC-803, HCT-116, and MCF-7 cells with IC values of 1.38, 5.34, and 5.21 µM, respectively. The structure-activity relationship of quinoline-chalcone derivatives was preliminarily explored in this report. Further mechanism studies suggested that compound inhibited MGC-803 cells in a dose-dependent manner and the cell colony formation activity of MGC-803 cells, arrested MGC-803 cells at the G2/M phase and significantly upregulated the levels of apoptosis-related proteins (Caspase3/9 and cleaved-PARP) in MGC-803 cells. In addition, compound could significantly induce ROS generation, and was dependent on ROS production to exert inhibitory effects on gastric cancer cells. Taken together, all the results suggested that directly linking chalcone fragment to the quinoline scaffold could produce novel anticancer molecules, and compound might be a valuable lead compound for the development of anticancer agents.
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http://dx.doi.org/10.3390/molecules26164899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398129PMC
August 2021

Drug Discovery Targeting Focal Adhesion Kinase (FAK) as a Promising Cancer Therapy.

Molecules 2021 Jul 13;26(14). Epub 2021 Jul 13.

Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

FAK is a nonreceptor intracellular tyrosine kinase which plays an important biological function. Many studies have found that FAK is overexpressed in many human cancer cell lines, which promotes tumor cell growth by controlling cell adhesion, migration, proliferation, and survival. Therefore, targeting FAK is considered to be a promising cancer therapy with small molecules. Many FAK inhibitors have been reported as anticancer agents with various mechanisms. Currently, six FAK inhibitors, including (Phase I), (Phase II), (Phase I), (Phase I), (Phase I), and (Phase I) are undergoing clinical trials in different phases. Up to now, there have been many novel FAK inhibitors with anticancer activity reported by different research groups. In addition, FAK degraders have been successfully developed through "proteolysis targeting chimera" (PROTAC) technology, opening up a new way for FAK-targeted therapy. In this paper, the structure and biological function of FAK are reviewed, and we summarize the design, chemical types, and activity of FAK inhibitors according to the development of FAK drugs, which provided the reference for the discovery of new anticancer agents.
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http://dx.doi.org/10.3390/molecules26144250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308130PMC
July 2021

Discovery of Novel Diarylamide -Containing Heterocyclic Derivatives as New Tubulin Polymerization Inhibitors with Anti-Cancer Activity.

Molecules 2021 Jul 2;26(13). Epub 2021 Jul 2.

Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Tubulin has been regarded as an attractive and successful molecular target in cancer therapy and drug discovery. Vicinal diaryl is a simple scaffold found in many colchicine site tubulin inhibitors, which is also an important pharmacophoric point of tubulin binding and anti-cancer activity. As the continuation of our research work on colchicine binding site tubulin inhibitors, we designed and synthesized a series of diarylamide -containing heterocyclic derivatives by the combination of vicinal diaryl core and -containing heterocyclic skeletons into one hybrid though proper linkers. Among of these compounds, compound containing a 5-methoxyindole group exhibited the most potent inhibitory activity against the tested three human cancer cell lines (MGC-803, PC-3 and EC-109) with IC values of 1.56 μM, 3.56 μM and 14.5 μM, respectively. Besides, the SARs of these compounds were preliminarily studied and summarized. The most active compound produced the inhibition of tubulin polymerization in a dose-dependent manner and caused microtubule network disruption in MGC-803 cells. Therefore, compound was identified as a novel tubulin polymerization inhibitor targeting the colchicine binding site. In addition, the results of molecular docking also suggested compound could tightly bind into the colchicine binding site of β-tubulin.
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http://dx.doi.org/10.3390/molecules26134047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272053PMC
July 2021

Enantioselective Synthesis of Fused Isocoumarins via Palladium-Catalyzed Annulation of Alkyne-Tethered Malononitriles.

J Org Chem 2021 Aug 13;86(15):10799-10811. Epub 2021 Jul 13.

Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), and College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China.

An enantioselective palladium-catalyzed annulation of alkyne-tethered malononitriles for the synthesis of 3,4-ring-fused isocoumarins is described. This cascade strategy involves oxypalladation of -alkynylbenzoates and desymmetrizing addition onto one cyano group of the pendant malononitriles, which enables the concurrent construction of two rings and an all-carbon quaternary stereocenter in a single operation.
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http://dx.doi.org/10.1021/acs.joc.1c01026DOI Listing
August 2021

Trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes.

Chem Sci 2021 Jan 7;12(9):3210-3215. Epub 2021 Jan 7.

Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University 299 Bayi Road Wuhan 430072 Hubei China

Vicinal trifluoromethyl azides have widespread applications in organic synthesis and drug development. However, their preparation is generally limited to transition-metal-catalyzed three-component reactions. We report here a simple and metal-free method that rapidly provides these building blocks from abundant alkenes and trifluoromethanesulfonyl azide (NSOCF). This unprecedented two-component reaction employs readily available NSOCF as a bifunctional reagent to concurrently incorporate both CF and N groups, which avoids the use of their expensive and low atom economic precursors. A wide range of functional groups, including bio-relevant heterocycles and amino acids, were tolerated. Application of this method was further demonstrated by scale-up synthesis (5 mmol), product derivatization to CF-containing medicinal chemistry motifs, as well as late-stage modification of natural product and drug derivatives.
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http://dx.doi.org/10.1039/d0sc06473dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179360PMC
January 2021

FeCl-Mediated Regioselective Aminochlorination and Aminoazidation of Styrenes with Trifluoromethanesulfonyl Azide.

Org Lett 2021 Jul 22;23(13):5102-5106. Epub 2021 Jun 22.

Sauvage Center for Molecular Sciences; Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education; College of Chemistry and Molecular Sciences, Wuhan University. 299 Bayi Road, Wuhan, Hubei 430072, China.

An efficient aminochlorination reaction of stryenes is described using NSOCF as an amination reagent and FeCl as a chloride source. The operationally simple procedure features mild reaction conditions, good functional group compatibility, and high regioselectivity. An example of aminobromination using FeBr is also realized. Additionally, a one-pot aminoazidation of styrenes is achieved by adding sodium azide to the reaction. The gram-scale synthesis and downstream derivatization of the products are showcased as well.
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http://dx.doi.org/10.1021/acs.orglett.1c01642DOI Listing
July 2021

Overcoming the rate-distance limit of device-independent quantum key distribution: erratum.

Opt Lett 2021 Jun;46(11):2609

In this Erratum the funding and references sections of Opt. Lett.46, 1632 (2021)OPLEDP0146-959210.1364/OL.417851 have been updated.
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http://dx.doi.org/10.1364/OL.428480DOI Listing
June 2021

Overcoming the rate-distance limit of device-independent quantum key distribution.

Opt Lett 2021 Apr;46(7):1632-1635

Device-independent quantum key distribution (DIQKD) exploits the violation of a Bell inequality to extract secure keys even if users' devices are untrusted. Currently, all DIQKD protocols suffer from the secret key capacity bound, i.e., the secret key rate scales linearly with the transmittance of two users. Here we propose a heralded DIQKD scheme based on entangled coherent states to improve entangling rates whereby long-distance entanglement is created by single-photon-type interference. The secret key rate of our scheme can significantly outperform the traditional two-photon-type Bell-state measurement scheme and, importantly, surpass the above capacity bound. Our protocol therefore is an important step towards a realization of DIQKD and can be a promising candidate scheme for entanglement swapping in the future quantum internet.
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http://dx.doi.org/10.1364/OL.417851DOI Listing
April 2021

Enantioselective Synthesis of α-All-Carbon Quaternary Center-Containing Carbazolones via Amino-palladation/Desymmetrizing Nitrile Addition Cascade.

J Am Chem Soc 2021 03 8;143(10):3734-3740. Epub 2021 Mar 8.

Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), and College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, Hubei, China.

An enantioselective Pd(II)-catalyzed amino-cyclization and desymmetrizing nitrile addition cascade reaction of alkyne-tethered malononitriles is reported. This reaction forms two rings and one quaternary carbon center in a single step and serves as an efficient strategy for the construction of α-quaternary carbazolones with high enantioselectivities (up to 98:2 er). The utility of this method is demonstrated by product derivatization into a diverse array of heterocycles and a nitrile-containing leucomidine A analog.
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http://dx.doi.org/10.1021/jacs.1c00840DOI Listing
March 2021

The AMPAR antagonist perampanel protects the neurovascular unit against traumatic injury via regulating Sirt3.

CNS Neurosci Ther 2021 01 9;27(1):134-144. Epub 2021 Jan 9.

Department of Neurosurgery, The 904th Hospital of PLA, Medical School of Anhui Medical University, Wuxi, China.

Introduction: Perampanel is a highly selective and noncompetitive α-amino-3 -hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) antagonist, which has been used as an orally administered antiepileptic drug in more than 55 countries. Recently, perampanel was shown to exert neuroprotective effects in hemorrhagic and ischemic stroke models via regulating blood-brain barrier (BBB) function.

Aim: Here, the protective effects of perampanel were investigated in an in vitro neurovascular unit (NVU) system established using a triple cell co-culture model (neurons, astrocytes, and brain microvascular endothelial cells) and in an in vivo traumatic brain injury (TBI) model.

Results: Neurons in the NVU system exhibit a more mature morphological phenotype compared with neurons cultured alone, and the co-culture system mimicked an impermeable barrier in vitro. Perampanel protects the NVU system against traumatic and excitotoxic injury, as evidenced by reduced lactate dehydrogenase (LDH) release and apoptotic rate. Treatment with perampanel attenuated lipid peroxidation and expression of inflammatory cytokines. In addition, perampanel increased Sirt3 protein expression, enhanced the activities of mitochondrial enzyme IDH2 and SOD2, and preserved BBB function in vitro. Knockdown of Sirt3 using specific siRNA (Si-Sirt3) partially reserved the effects of perampanel on neuronal injury and BBB function. Treatment with perampanel in vivo attenuated brain edema, preserved neurological function, inhibited apoptosis and microglia activation after TBI. Furthermore, perampanel increased the expression of Sirt3 and preserved BBB function after TBI. The effect of perampanel on BBB function and brain edema was abolished by knockdown of Sirt3 in vivo.

Conclusion: Our results indicate that the noncompetitive AMPAR antagonist perampanel protects the NVU system and reduces brain damage after TBI via activating the Sirt3 cascades.
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http://dx.doi.org/10.1111/cns.13580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804923PMC
January 2021

Single-cell RNA sequencing reveals regulation of fetal ovary development in the monkey (Macaca fascicularis).

Cell Discov 2020 Dec 29;6(1):97. Epub 2020 Dec 29.

Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, CAS Key Laboratory of Primate Neurobiology, Chinese Academy of Sciences, 200031, Shanghai, China.

Germ cells are vital for reproduction and heredity. However, the mechanisms underlying female germ cell development in primates, especially in late embryonic stages, remain elusive. Here, we performed single-cell RNA sequencing of 12,471 cells from whole fetal ovaries, and explored the communications between germ cells and niche cells. We depicted the two waves of oogenesis at single-cell resolution and demonstrated that progenitor theca cells exhibit similar characteristics to Leydig cells in fetal monkey ovaries. Notably, we found that ZGLP1 displays differentially expressed patterns between mouse and monkey, which is not overlapped with NANOG in monkey germ cells, suggesting its role in meiosis entry but not in activating oogenic program in primates. Furthermore, the majority of germ cell clusters that sharply express PRDM9 and SPO11 might undergo apoptosis after cyst breakdown, leading to germ cell attrition. Overall, our work provides new insights into the molecular and cellular basis of primate fetal ovary development at single-cell resolution.
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http://dx.doi.org/10.1038/s41421-020-00219-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769980PMC
December 2020

Glial cell induced neural differentiation of bone marrow stromal cells.

Open Med (Wars) 2020 30;15(1):954-961. Epub 2020 Sep 30.

School of Life Science and Biotechnology, Dalian University of Technology, No. 2 Linggong Road, Dalian 116023, Liaoning Province, China.

Background: Bone marrow stromal cells (BMSCs) have an important application prospect in the field of cell therapy for various neurodegenerative diseases, and inducing factors that regulate BMSC differentiation are proposed as a promising therapeutic strategy. In this study, we explored the effect of glial cell-derived neurotrophic factor (GDNF) on the course of BMSC differentiation.

Methods: BMSCs were isolated from rat bone marrow and induced by GDNF. The effects of GDNF on BMSC viability and proliferation were verified by cell counting kit-8, MTT, bromodeoxyuridine, and flow cytometry assays. Neuronal differentiation from BMSCs was detected by quantitative real-time polymerase chain reaction and immunofluorescence via measuring the expression of several neural specific markers.

Results: Compared to untreated BMSCs, GDNF induced the differentiation of BMSCs into neuron-like cells and enhanced the expression levels of neuronal markers including nestin and NCAM. Moreover, the expression of SCF was suppressed by GDNF stimulation.

Conclusion: GDNF could elevate the differentiation of BMSCs into neuron-like cells and could be considered as an effective candidate cell for future neuroscience research.
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http://dx.doi.org/10.1515/med-2020-0229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712328PMC
September 2020

The methylation status in GNAS clusters May Be an epigenetic marker for oocyte quality.

Biochem Biophys Res Commun 2020 12 24;533(3):586-591. Epub 2020 Sep 24.

Fertility Preservation Lab, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China. Electronic address:

During follicle growth, DNA methylation is gradually established, which is important for oocyte developmental competence. Due to the facts that oocytes from prepubertal individuals show reduced developmental outcomes when compared to those from sexually mature individuals, and the fact that oocytes derived from in vitro follicle culture have much lower developmental competence, it is worth exploring whether prepubertal superovulation and in vitro follicle culture will cause changes in DNA methylation imprinting status in oocytes. In this study, we found that the CpG island in maternally imprinted GNAS clusters was hypermethylated in the MII-stage oocytes from sexually mature mice, but was hypomethylated in oocytes from prepuberty individuals. The GNAS clusters in the MII-stage oocytes obtained by in vitro follicle culture showed heterogeneous methylation levels, indicating different qualities of oocytes, however, three other maternally imprinted genes, Peg1, Lot1 and Impact, were all hypermethylated in the MII-stage oocytes derived from both prepubertal superovulation and in vitro follicle culture. Taken together, the findings suggest that the methylation status in GNAS clusters may potentially represent a novel epigenetic marker for oocyte quality detection.
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http://dx.doi.org/10.1016/j.bbrc.2020.09.055DOI Listing
December 2020

Pd-catalyzed arylation/aza-Michael addition cascade to C2-spiroindolines and azabicyclo[3.2.2]nonanones.

Chem Commun (Camb) 2020 Oct 9;56(80):12013-12016. Epub 2020 Sep 9.

Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China.

A palladium-catalyzed arylation/aza-Michael addition cascade reaction of β-substituted cyclic enones and 2-haloanilines has been reported. Using 1 mol% Pd(PPh) as a catalyst, C2-spiroindolines are accessed via an intermolecular vinylogous arylation of β-alkyl cyclic enones and 2-haloanilines followed by an intramolecular aza-Michael addition. The functional group tolerance of this transformation is examined by 18 examples in up to 93% yield. In the second part, we developed an α'-arylation/aza-Michael addition cascade strategy to construct azabicyclo[3.2.2]nonanones catalyzed by Pd(MeCN)Cl·PPh. This study provides a quick route to complex and useful spiro- and bridged-heterocycles from readily available starting materials in good yields with high regioselectivity.
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http://dx.doi.org/10.1039/d0cc04935bDOI Listing
October 2020

DNA methylation establishment of CpG islands near maternally imprinted genes on chromosome 7 during mouse oocyte growth.

Mol Reprod Dev 2020 Jun 17. Epub 2020 Jun 17.

Fertility Preservation Lab, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, China.

The genome methylation is globally erased in early fetal germ cells, and it is gradually re-established during gametogenesis. The expression of some imprinted genes is regulated by the methylation status of CpG islands, while the exact time of DNA methylation establishment near maternal imprinted genes during oocyte growth is not well known. Here, growing oocytes were divided into three groups based on follicle diameters including the S-group (60-100 μm), M-group (100-140 μm), and L-group (140-180 μm). The fully grown germinal vesicle (GV)-stage and metaphase II (M2)-stage mature oocytes were also collected. These oocytes were used for single-cell bisulfite sequencing to detect the methylation status of CpG islands near imprinted genes on chromosome 7. The results showed that the CpG islands near Ndn, Magel2, Mkrn3, Peg12, and Igf2 were completely unmethylated, but those of Peg3, Snrpn, and Kcnq1ot1 were hypermethylated in MII-stage oocytes. The methylation of CpG islands near different maternal imprinted genes occurred asynchronously, being completed in later-stage growing oocytes, fully grown GV oocytes, and mature MII-stage oocytes, respectively. These results show that CpG islands near some maternally imprinted genes are not necessarily methylated, and that the establishment of methylation of other maternally imprinted genes is completed at different stages of oocyte growth, providing a novel understanding of the establishment of maternally imprinted genes in oocytes.
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http://dx.doi.org/10.1002/mrd.23395DOI Listing
June 2020

Enantioselective Assembly of Cycloenones with a Nitrile-Containing All-Carbon Quaternary Center from Malononitriles Enabled by Ni Catalysis.

J Am Chem Soc 2020 04 13;142(16):7328-7333. Epub 2020 Apr 13.

Sauvage Center for Molecule Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, 299 Bayi Road, Wuhan 430072, Hubei, China.

Chiral nitriles are valuable molecules in modern organic synthesis and drug discovery. Selectively differentiating the two nitrile groups of widely available malononitrile derivatives is a straightforward yet underdeveloped route to construct enantioenriched nitriles. Here we report an enantioselective nickel-catalyzed desymmetrization of malononitriles for the generation of nitrile-containing all-carbon quaternary stereocenters. This protocol involves a nickel-catalyzed addition of aryl boronic acids to alkynes, followed by a selective nitrile insertion, providing unprecedented access to enantioenriched 5-7-membered α-cyano-cycloenones with a fully substituted olefin from a broad range of substrates. The synthetic utility of these nitrile products is demonstrated by gram-scale synthesis and conversion to several useful functional groups.
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http://dx.doi.org/10.1021/jacs.0c02075DOI Listing
April 2020

Enantioselective Iron/Bisquinolyldiamine Ligand-Catalyzed Oxidative Coupling Reaction of 2-Naphthols.

Molecules 2020 Feb 14;25(4). Epub 2020 Feb 14.

Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China.

An iron-catalyzed asymmetric oxidative homo-coupling of 2-naphthols for the synthesis of 1,1'-Bi-2-naphthol (BINOL) derivatives is reported. The coupling reaction provides enantioenriched BINOLs in good yields (up to 99%) and moderate enantioselectivities (up to 81:19 er) using an iron-complex generated in situ from Fe(ClO) and a bisquinolyldiamine ligand [(1,2)-,-di(quinolin-8-yl)cyclohexane-1,2-diamine, ]. A number of ligands (-) and the analogs of , with various substituents and chiral backbones, were synthesized and examined in the oxidative coupling reactions.
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http://dx.doi.org/10.3390/molecules25040852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070846PMC
February 2020

Synthesis of 2,3-Ring Fused Pyrroles via Cu-Catalyzed 5--dig Annulation of Alkyne-Tethered Enaminones.

J Org Chem 2019 Dec 21;84(23):15754-15763. Epub 2019 Nov 21.

Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, College of Chemistry and Molecular Sciences , Wuhan University , Wuhan , Hubei 430072 , China.

A copper-catalyzed annulation of alkyne-tethered enaminones for the synthesis of 2,3-ring fused pyrroles is reported. The 5--dig cyclization/olefin migration reaction delivers the multisubstituted pyrroles in 59-99% yields with 16 examples. This strategy features easily available starting materials, mild reaction conditions, and a cheap ligand-free copper catalyst. The atom-economic transformation provides a simple access to a variety of synthetic useful pyrroles and their derivatives.
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http://dx.doi.org/10.1021/acs.joc.9b02672DOI Listing
December 2019

Enantioselective Synthesis of β-Quaternary Carbon-Containing Chromanes and 3,4-Dihydropyrans via Cu-Catalyzed Intramolecular C-O Bond Formation.

Org Lett 2019 Nov 23;21(21):8852-8856. Epub 2019 Oct 23.

Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, Sauvage Center for Molecular Sciences, College of Chemistry and Molecular Sciences , Wuhan University , Wuhan , Hubei 430072 , China.

A copper-catalyzed efficient enantioselective construction of chiral quaternary carbon-containing chromanes and 3,4-dihydropyrans is reported. The desymmetric C-O coupling is enabled by a chiral dimethylcyclohexane-1,2-diamine ligand and provides the desired products in good yields with high enantioselectivities. This method presents a broad substrate scope and is applicable to diversely substituted aryl bromides and alkenyl bromides. The application is demonstrated by a gram-scale synthesis and derivatization of the products toward valuable building blocks.
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http://dx.doi.org/10.1021/acs.orglett.9b03549DOI Listing
November 2019

Expression of ALDH1A1 and CD133 is associated with the prognosis and effect of different chemotherapeutic regimens in gastric cancer.

Oncol Lett 2019 Nov 4;18(5):4573-4582. Epub 2019 Sep 4.

Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.

Gastric cancer (GC) is one of the most common malignant tumors worldwide. Previous studies have reported that aldehyde dehydrogenase-1A1 (ALDH1A1) and cluster of differentiation (CD)-133 are considered to be cancer stem cell markers in GCs. The present study immunohistochemically examined the distribution and expression of two tumor stem cell markers, CD133 and ALDH1A1, in both primary tumors and para-tumor tissues. In 91 cases with stage III, 57 (62%) were positive for ALDH1A1 and 60 (66%) were positive for CD133. ALDH1A1 was detected in para-tumors and cancerous tissues of the stomach, and the immunoreactivity of the tumors was stronger than that in para-tumor tissues. CD133 was only detected in tumors. The expression of ALDH1A1 was significantly associated with advanced T/N stage (T stage, P=0.012; N stage, P=0.023) and poor differentiation (P=0.020), while CD133 was associated with advanced T stage (P=0.007). Univariate and multivariate Cox proportional hazards analysis revealed that tumor stage, CD133 expression, vascular invasion and sex were independent predictors of disease-free survival (DFS) time, and tumor size, vascular invasion and sex were independent predictors of overall survival (OS) time in patients with GC. Patients with CD133 GC had poorer DFS (P=0.042), while ALDH1A1 GC was not associated with poorer DFS. In regard to chemotherapy, improvements in survival were not observed after the addition of taxane compared with two-drug therapy. However, the subgroup analysis indicated that in the ALDH1A1 subgroup, and CD133 and ALDH1A1 subgroups, an increased OS was observed in two-drug therapy (P=0.043). The results of the present study indicate that ALDH1A1 and CD133 may play an important role in tumor invasion, metastasis and prognosis, and ALDH1A1 expression does not benefit the taxane-based triple chemotherapeutic regimen in patients with GC.
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http://dx.doi.org/10.3892/ol.2019.10798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781782PMC
November 2019

Detosylative (Deutero)alkylation of Indoles and Phenols with (Deutero)alkoxides.

Org Lett 2019 09 23;21(17):7073-7077. Epub 2019 Aug 23.

Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, Sauvage Center for Molecular Sciences, College of Chemistry and Molecular Sciences, Wuhan University, 299 Bayi Road, Wuhan, Hubei 430072, China.

An efficient strategy for N/O-(deutero)alkylation of indoles and phenols with alkoxides/alcohols as the alkylation reagents is described. The consecutive detosylation/alkylation transformations feature mild reaction conditions, high -selectivity, and good functional group tolerance (>50 examples). A one-pot selective N-alkylation of unprotected indoles with alcohols and TsCl is also realized. The application of this method is demonstrated by the introduction of isotope-labeled (CD and CH) groups using the readily accessible labeled alcohols and the synthesis of pharmaceuticals.
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http://dx.doi.org/10.1021/acs.orglett.9b02639DOI Listing
September 2019

Synthesis of Sultams and Cyclic -Sulfonyl Ketimines via Iron-Catalyzed Intramolecular Aliphatic C-H Amidation.

Org Lett 2019 08 12;21(15):5808-5812. Epub 2019 Jul 12.

Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, College of Chemistry and Molecular Sciences , Wuhan University , Wuhan , Hubei 430072 , China.

Cyclic sulfonamides (sultams) play a unique role in drug discovery and synthetic chemistry. A direct synthesis of sultams by an intramolecular C(sp)-H amidation reaction using an iron complex in situ derived from Fe(ClO) and aminopyridine ligand is reported. This strategy features a readily available catalyst and tolerates a broad variety of substrates as demonstrated by 22 examples (up to 89% yield). A one-pot iron-catalyzed amidation/oxidation procedure for the synthesis of cyclic -sulfonyl ketimines is also realized with up to 92% yield (eight examples). The synthetic utility of the method is validated by a gram-scale reaction and derivatization of the products to ring-fused sultams.
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http://dx.doi.org/10.1021/acs.orglett.9b01732DOI Listing
August 2019

Cu-Catalyzed Arylation/Acyl Migration Cascade Reaction of Enaminones: Access to N-Fused Polycyclic and 2,3-Disubstituted Indoles.

J Org Chem 2019 06 10;84(12):7995-8005. Epub 2019 Jun 10.

Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, College of Chemistry and Molecular Sciences , Wuhan University , 299 Bayi Road , Wuhan 430072 , Hubei , China.

An efficient synthesis of N-fused polycyclic and 2,3-disubstituted indoles by copper-catalyzed direct annulation/acyl migration reaction of enaminones is reported. This strategy features cheap and low loading of the catalyst/ligand, readily available starting materials, and good functional group compatibilities. Notably, allyl-containing substrates are also tolerated, which allows the downstream derivatization toward indole alkaloids.
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http://dx.doi.org/10.1021/acs.joc.9b00866DOI Listing
June 2019

Iron-Catalyzed Intramolecular Amination of Aliphatic C-H Bonds of Sulfamate Esters with High Reactivity and Chemoselectivity.

Org Lett 2019 04 9;21(8):2673-2678. Epub 2019 Apr 9.

Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, College of Chemistry and Molecular Sciences , Wuhan University . 299 Bayi Road , Wuhan , Hubei 430072 , China.

It is challenging to develop simple and low cost catalytic systems while maintaining high reactivity and selectivity. An iron-catalyzed intramolecular C-H amination of sulfamate esters using simple and cheap ligands is reported with general substrate scope (31 examples, up to 95% yield). The addition of second ligand, bipyridine, is able to accelerate the reaction and increase the yield. The ready availability of these iron catalysts provides a promising approach to selective introduction of nitrogen into hydrocarbon feedstock.
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http://dx.doi.org/10.1021/acs.orglett.9b00660DOI Listing
April 2019

Synthesis of N-Fused Polycyclic Indoles via Ligand-Free Palladium-Catalyzed Annulation/Acyl Migration Reaction.

Org Lett 2019 02 29;21(4):1082-1086. Epub 2019 Jan 29.

Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, College of Chemistry and Molecular Sciences , Wuhan University , 299 Bayi Road , Wuhan , Hubei 430072 , China.

An efficient synthesis of N-fused polycyclic indoles by a palladium-catalyzed annulation/acyl migration cascade reaction is described. The reaction is ligand-free, scalable, and provides access to a diverse range of useful indole scaffolds from readily available starting materials. Supporting mechanistic studies indicate that the reaction likely proceeds via an intramolecular α-arylation mechanism. The synthetic utility of this protocol is demonstrated by a gram-scale reaction and syntheses toward indole alkaloids and a HSP90 inhibitor.
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http://dx.doi.org/10.1021/acs.orglett.8b04128DOI Listing
February 2019

General and Practical Potassium Methoxide/Disilane-Mediated Dehalogenative Deuteration of (Hetero)Arylhalides.

J Am Chem Soc 2018 09 22;140(35):10970-10974. Epub 2018 Aug 22.

Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, College of Chemistry and Molecular Sciences , Wuhan University , 299 Bayi Road , Wuhan , Hubei 430072 , China.

Herein we describe a general, mild and scalable method for deuterium incorporation by potassium methoxide/hexamethyldisilane-mediated dehalogenation of arylhalides. With CDCN as a deuterium source, a wide array of heteroarenes prevalent in pharmaceuticals and bearing diverse functional groups are labeled with excellent deuterium incorporation (>60 examples). The ipso-selectivity of this method provides precise access to libraries of deuterated indoles and quinolines. The synthetic utility of our method has been demonstrated by the incorporation of deuterium into complex natural and drug-like compounds.
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http://dx.doi.org/10.1021/jacs.8b07597DOI Listing
September 2018

The MKK7 inhibitor peptide GADD45β-I attenuates ER stress-induced mitochondrial dysfunction in HT22 cells: Involvement of JNK-Wnt pathway.

Brain Res 2018 07 21;1691:1-8. Epub 2018 Apr 21.

Basic Medical Sciences Research Center, Shaanxi Fourth People's Hospital, Xi'an, Shaanxi 710043, China. Electronic address:

JNK, a member of the mitogen activated protein kinases (MAPKs) superfamily, plays a key role in cell death in many neurological disorders, but systemic inhibition of JNK has detrimental side effects. JNK can be regulated by two direct upstream kinases: MAPK kinase 4 (MKK4) and MAPK kinase 7 (MKK7). Here, we investigated the effect of GADD45β-I, a recently designed cell-permeable inhibitor peptide for MKK7, on endoplasmic reticulum (ER) stress-induced cytotoxicity in neuronal HT22 cells. We found that treatment with the ER stress inducer tunicamycin (TM) increased the phosphorylation of JNK and MKK7 in HT22 cells, which was nullified by GADD45β-I. GADD45β-I significantly attenuated TM-induced toxicity via inhibiting apoptotic cell death, as evidenced by decreased number of TUNEL-positive cells and reduced caspase-3 activity. GADD45β-I treatment also decreased expression of ER stress associated pro-apoptotic proteins and prevented morphological changes of the ER after TM exposure. In addition, inhibition of mitochondrial oxidative stress and preservation of intracellular ATP levels were observed in GADD45β-I-treated cells. The experiments using siRNA transfection and Topflash reporter assay revealed a possible involvement of Wnt/β-catenin pathway in GADD45β-I-induced protection in HT22 cells. In summary, our results demonstrated that GADD45β-I exerted protective effects against TM-induced cytotoxicity via regulating JNK-Wnt pathway. Targeting MKK7 could represent a new therapeutic strategy for the treatment of neurological diseases where ER stress associated neuronal injury are involved.
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http://dx.doi.org/10.1016/j.brainres.2018.04.012DOI Listing
July 2018

Functional analysis of a regulator of G-protein signaling CgRGS1 in the rubber tree anthracnose fungus Colletotrichum gloeosporioides.

Arch Microbiol 2018 Apr 25;200(3):391-400. Epub 2017 Nov 25.

Institute of Tropical Agriculture and Forestry, Hainan University, Haikou, 570228, China.

Colletotrichum gloeosporioides is the causal agent of rubber anthracnose, which is also one of the important biological factors threatening the development of natural rubber industry in the world. Regulators of G-protein signaling (RGS) are key negative regulators of G-proteins, which play important roles in growth, development and pathogenic processes of plant pathogens. In this study, a RGS gene CgRGS1 was functionally characterized in C. gloeosporioides. Compared to the wild type, the CgRGS1 deletion mutant had slow vegetative growth, reduced conidia with multi-end germination, low appressorium formation rate, high resistance to oxidative stress and SDS. Moreover, the mutant was sensitive to osmotic pressure and showed decreased virulence. In conclusion, CgRGS1 is involved in regulation of vegetative growth, conidiation, germination, appressorium formation, oxidative stress, osmotic pressure response and pathogenicity in C. gloeosporioides.
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http://dx.doi.org/10.1007/s00203-017-1455-1DOI Listing
April 2018
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