A5070154658- Catalytic C–H Functionalization Methods
- Synthesis and Catalytic Reactions
- Protein Degradation and Inhibitors
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Catalytic Cross-Coupling Reactions
- Cyclopropane Reaction Mechanisms
- Ubiquitin and proteasome pathways
- Asymmetric Hydrogenation and Catalysis
- Multiple Myeloma Research and Treatments
- Sulfur-Based Synthesis Techniques
- Oxidative Organic Chemistry Reactions
- Catalytic Alkyne Reactions
- Crystallography and molecular interactions
- Synthetic Organic Chemistry Methods
- Asymmetric Synthesis and Catalysis
- Histone Deacetylase Inhibitors Research
- Chemical Synthesis and Analysis
- Carbon dioxide utilization in catalysis
- Peptidase Inhibition and Analysis
- Alkaloids: synthesis and pharmacology
- ATP Synthase and ATPases Research
- Polyomavirus and related diseases
- CAR-T cell therapy research
- Natural Compounds in Disease Treatment
Chinese Academy of Sciences
2016-2025
Shenzhen Third People’s Hospital
2014-2025
Southern University of Science and Technology
2022-2025
Institute of Zoology
2025
National Clinical Research
2022-2025
Second Xiangya Hospital of Central South University
2025
Xiangya Hospital Central South University
2025
Shanghai Institute of Materia Medica
2015-2024
University of Chinese Academy of Sciences
2016-2024
Nanjing University of Chinese Medicine
2021-2024
Abstract The pandemic caused by emerging coronavirus SARS-CoV-2 presents a serious global public health emergency in urgent need of prophylactic and therapeutic interventions. cellular entry depends on binding between the viral Spike protein receptor-binding domain (RBD) angiotensin converting enzyme 2 (ACE2) target cell receptor. Here, we report isolation characterization 206 RBD-specific monoclonal antibodies (mAbs) derived from single B cells eight infected individuals. These mAbs come...
The bromodomain and extra-terminal (BET) family proteins, consisting of BRD2, BRD3, BRD4, testis-specific BRDT members, are epigenetic "readers" play a key role in the regulation gene transcription. BET proteins considered to be attractive therapeutic targets for cancer other human diseases. Recently, heterobifunctional small-molecule degraders have been designed based upon proteolysis targeting chimera (PROTAC) concept induce protein degradation. Herein, we present our design, synthesis,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereochemical control of yeast reductions. 1. Asymmetric synthesis L-carnitineBing Nan Zhou, Aravamudan S. Gopalan, Frank VanMiddlesworth, Woan Ru Shieh, and Charles J. SihCite this: Am. Chem. Soc. 1983, 105, 18, 5925–5926Publication Date (Print):September 1, 1983Publication History Published online1 May 2002Published inissue 1 September 1983https://pubs.acs.org/doi/10.1021/ja00356a041https://doi.org/10.1021/ja00356a041research-articleACS...
Proteins of the bromodomain and extra-terminal (BET) family are epigenetics "readers" promising therapeutic targets for cancer other human diseases. We describe herein a structure-guided design [1,4]oxazepines as new class BET inhibitors our subsequent design, synthesis, evaluation proteolysis-targeting chimeric (PROTAC) small-molecule degraders. Our efforts have led to discovery extremely potent degraders, exemplified by QCA570, which effectively induces degradation proteins inhibits cell...
Triple-negative breast cancers (TNBC) remain clinically challenging with a lack of options for targeted therapy. In this study, we report the development second-generation BET protein degrader, BETd-246, which exhibits superior selectivity, potency, and antitumor activity. human TNBC cells, BETd-246 induced degradation proteins at low nanomolar concentrations within 1 hour exposure, resulting in robust growth inhibition apoptosis. was more potent effective cells than its parental inhibitor...
The rhodium-catalyzed intermolecular direct C-H thiolation of arenes with aryl and alkyl disulfides was developed for the first time to provide a convenient route thioethers. This strategy is compatible many different directing groups exhibits excellent functional group tolerance. More significantly, mono- or dithiolation can be selectively achieved, thus providing straightforward way selective preparation thioethers dithioethers.
Abstract A Rh III ‐catalyzed procedure for the C7‐selective CH alkylation of various indolines with α‐diazo compounds at room temperature is reported. The advantages this process are: 1) simple, mild, and pH‐neutral reaction conditions, 2) broad substrate scope, 3) complete regioselectivity, 4) no need an external oxidant, 5) N 2 as sole byproduct. Furthermore, bis‐alkylation carbazoles C1 C8 positions have also been developed. More significantly, first time, a successful Ir intermolecular...
A rhodium-catalyzed oxidative C2-acylation of indoles with aryl and alkyl aldehydes via C–H bond activation is described. The reaction highly atom-economic provides easy access to a wide variety 2-aroylindoles.
Abstract An unprecedented rhodium(III)‐catalyzed regioselective redox‐neutral annulation reaction of 1‐naphthylamine N‐oxides with diazo compounds was developed to afford various biologically important 1 H ‐benzo[g]indolines. This coupling proceeds under mild conditions and does not require external oxidants. The only by‐products are dinitrogen water. More significantly, this represents the first example dual functiaonalization unactivated a primary C(sp 3 )H bond 2 diazocarbonyl compounds....
Direct C-2 amidation of indoles was reported using sulfonyl azides as the amino source to release N(2) single byproduct. This reaction exhibits high functional group tolerance and regioselectivity, providing a variety 2-amino substituted in excellent yield. The procedure is robust, reliable, compatible with water air.
A Rh(III)-catalyzed unsymmetrical C-H alkylation and amidation of N-phenoxyacetamides with diazo compounds has been developed under mild redox-neutral conditions, producing dinitrogen as the only byproduct. The reaction represents first example one-step, difunctionalization two ortho-C-H bonds. Experimental computational studies support that most likely undergo an initial via a activation, resulting Rh(III) intermediate subsequently undergoes intramolecular oxidative addition into O-N bond...
Abstract The rhodium(III)‐catalyzed [3+2] CH cyclization of aniline derivatives and internal alkynes represents a useful contribution to straightforward synthesis indoles. However, there is no report on the more challenging pharmaceutically important N ‐hydroxyindoles 3 H ‐indole‐ ‐oxides. Reported herein first [4+1] oxidative nitrones with diazo compounds access More significantly, this reaction proceeds at room temperature has been extended ‐hydroxyindolines.
Going green! The rhodium(III)-catalyzed annulation of aryl ketone O-methyl oximes with isocyanates for the synthesis 3-methyleneisoindolin-1-ones is reported (see scheme). This reaction exhibits high regioselectivity, functional-group tolerance, and broad substrate scope, without use additives or production environmentally hazardous waste.
Abstract Targeting epigenetics in cancer has emerged as a promising anticancer strategy. p300/CBP is central regulator of and plays an important role hepatocellular carcinoma (HCC) progression. Tumor-associated metabolic alterations contribute to the establishment maintenance tumorigenic state. In this study, we used novel p300 inhibitor, B029-2, investigate effect targeting HCC tumor metabolism. p300/CBP–mediated acetylation H3K18 H3K27 increased tissues compared with surrounding...
p300 and CREB-binding protein (CBP) are ubiquitously expressed pleiotropic lysine acetyltransferases play a key role as transcriptional co-activators that essential for multitude of cellular processes. Despite great importance, there is lack highly selective, potent, druglike p300/CBP inhibitors. Through the artificial-intelligence-assisted drug discovery pipeline further optimization, we reported novel, potent small-molecule inhibitors histone (HAT) with desired properties, exemplified by...
A Rh(III)-catalyzed intramolecular redox-neutral or oxidative annulation of a tethered alkyne has been developed to efficiently construct 3,4-fused indoles via C–H activation pathway. The advantages this process are (1) ready availability precursors; (2) broad substrate scope; (3) complete regioselectivity; (4) simple and mild reaction conditions; (5) no need for an external oxidant employ molecular oxygen as the stoichiometric terminal oxidant.
An exoselective copper-catalyzed arylation- and vinylation-carbocyclization of electron-deficient alkenes was developed to provide rapid efficient access a variety functionalized 3,3-disubstituted oxindoles. With this method, highly concise formal synthesis (±)-physostigmine (±)-physovenine has been completed.
Small-molecule inhibitors of bromodomain and extra terminal proteins (BET), including BRD2, BRD3, BRD4 have therapeutic potential for the treatment human cancers other diseases conditions. In this paper, we report design, synthesis, evaluation γ-carboline-containing compounds as a new class small-molecule BET inhibitors. The most potent inhibitor (compound 18, RX-37) obtained from study binds to (BRD2, BRD4) with Ki values 3.2-24.7 nM demonstrates high selectivity over non-BET...
Abstract The autophagic ubiquitin‐like protein LC3 functions through interactions with LC3‐interaction regions (LIRs) of other autophagy proteins, including receptors, which stands out as a promising protein–protein interaction (PPI) target for the intervention autophagy. Post‐translational modifications like acetylation Lys49 on LIR‐interacting surface could disrupt interaction, offering an opportunity to design covalent small molecules interfering interface. Through screening compounds, we...
CH activation: A RhIII-catalyzed direct aldehyde amidation has been achieved with sulfonyl, aryl, and alkyl azides as the amine sources, release of N2 only byproduct (see scheme). More importantly, this catalytic reaction proceeds in absence external oxidants or additives, under mild conditions, at neutral pH air. This represents a new avenue for practical intermolecular CN bond formation by activation. Cp*=1,2,3,4,5-Pentamethylcyclopentadiene
The rhodium-catalyzed addition of an alkenyl C-H bond to isocyanates via sp(2) activation followed by intramolecular cyclization is described. This atom-economic and catalytic reaction affords a simple straightforward access biologically relevant 5-ylidene pyrrol-2(5H)-ones can be carried out under mild neutral conditions in the absence any additives environmentally hazardous waste production.
An iridium-catalyzed direct C-7 selective C-H alkynylation of indolines at room temperature, for the first time, has been developed via bond activation. Furthermore, example carbazoles C1 position is also achieved. More importantly, resulting product can be readily transformed into C7-alkynylated indoles, further widening derivatization indoles and highlighting synthetic utility this methodology.
An unprecedented Rh(III)-catalyzed direct intermolecular C–H amidation with N-hydroxycarbamates has been developed. Different directing groups, such as pyridine, pyrimidine, pyrazole, and N-OMe oxime, can be employed in this process, providing valuable N-carbamate-protected arylamines (e.g., Cbz, Moz, Ac, Boc, Fmoc). More importantly, process may afford a new avenue for where readily available used the nitrogen source
Abstract The rhodium‐catalyzed oxidative ortho ‐acylation of aryl ketone O ‐methyl oximes with and alkyl aldehydes via CH bond activation is described. cross‐coupling reaction exhibits high functional group tolerance regioselectivity under relatively mild conditions constitutes a versatile route to diverse library diaryl ketones, which are difficult obtain by the classical Friedel–Crafts acylation. Moreover, this proceeds an unprecedented Rh‐catalyzed highly electron‐deficient followed...