A5001164647- Asymmetric Synthesis and Catalysis
- Chemical Synthesis and Analysis
- Asymmetric Hydrogenation and Catalysis
- Chemical Synthesis and Reactions
- HIV/AIDS drug development and treatment
- Hepatitis C virus research
- Synthetic Organic Chemistry Methods
- Porphyrin and Phthalocyanine Chemistry
- Oxidative Organic Chemistry Reactions
- Metal-Catalyzed Oxygenation Mechanisms
- Axial and Atropisomeric Chirality Synthesis
- Synthesis and Biological Evaluation
- Fluorine in Organic Chemistry
- Synthesis and Catalytic Reactions
- Monoclonal and Polyclonal Antibodies Research
- Organic and Inorganic Chemical Reactions
- Sulfur-Based Synthesis Techniques
- Carbohydrate Chemistry and Synthesis
- Synthesis of heterocyclic compounds
- Metal complexes synthesis and properties
- Cyclopropane Reaction Mechanisms
- Coordination Chemistry and Organometallics
- Advanced Synthetic Organic Chemistry
- Catalytic C–H Functionalization Methods
- Multicomponent Synthesis of Heterocycles
China State Construction Engineering (China)
2024
Hunan Software Vocational Institute
2024
Brandeis University
2017-2023
Dana-Farber Cancer Institute
2021-2023
Southwestern Medical Center
2022
The University of Texas Southwestern Medical Center
2022
WuXi AppTec (China)
2006-2021
Harvard University
2021
Xi'an Institute of Optics and Precision Mechanics
2019
China Pharmaceutical University
2012-2018
Deubiquitinating enzymes (DUBs) are an emerging drug target class of ~100 proteases that cleave ubiquitin from protein substrates to regulate many cellular processes. A lack selective chemical probes impedes pharmacologic interrogation this important gene family. DUBs engage their cognate ligands through a myriad interactions. We embrace structural complexity tailor diversification strategy for DUB-focused covalent library. Pairing our library with activity-based profiling as high-density...
The NS5A protein plays a critical role in the replication of HCV and has been focus numerous research efforts over past few years. inhibitors have shown impressive vitro potency profiles replicon assays, making them attractive components for inclusion all oral combination regimens. Early work arena led to discovery our first clinical candidate, MK-4882 [2-((S)-pyrrolidin-2-yl)-5-(2-(4-(5-((S)-pyrrolidin-2-yl)-1H-imidazol-2-yl)phenyl)benzofuran-5-yl)-1H-imidazole]. While preclinical...
Catalytic asymmetric cross-coupling of imines constitutes a particularly desirable method for the synthesis chiral vicinal diamines directly from readily available achiral precursors. The potential this lies in possibility utilizing variety as reacting partners. However, realization highly stereoselective two different proved to be formidable challenge. Herein we report an unprecedented catalytic reaction that tolerates ketimines and aldimines nucleophiles electrophiles, respectively....
Novel planar chiral ferrocene nucleophilic catalysts (Fc-PIP) containing both central and elements were designed synthesized for catalytic enantioselective acyl transfer of secondary alcohols. A remarkably efficient catalyst with high selectivity factors (up to S = 1892) was identified. Comparing the combination chirality revealed a strong requirement "matched" elements, indicating that stereogenic center imidazole rings should present itself on same face as ferrocenyl fragment; otherwise,...
Abstract Novel cinchona alkaloid derived chiral phase‐transfer catalysts enabled the highly chemo‐, regio‐, diastereo‐, and enantioselective umpolung addition of trifluoromethyl imines to α,β‐unsaturated N ‐acyl pyrroles. With a catalyst loading ranging from 0.2 5.0 mol %, this new catalytic asymmetric transformation provides facile high‐yielding access enantiomerically enriched trifluoromethylated γ‐amino acids γ‐lactams.
This paper describes the mechanistic insight-guided development of a catalyst system, employing phenolic proton donor in addition to cinchonium-derived phase-transfer catalyst, control chemoselectivity two distinct intermediates, thereby enabling desired asymmetric tandem conjugate addition–protonation pathway dominate over number side-reaction pathways provide synthetic approach for direct generation optically active amines bearing nonadjacent stereocenters.
Cinchona alkaloid-derived chiral catalysts represent one of the most widely applied classes organocatalysts, which have been successfully utilized in promotion a wide variety asymmetric reactions. alkaloids exist nature as pseudoenantiomers, allow cinchona alkaloid-catalyzed reactions to provide high enantioselectivities and yields toward both enantiomers interest many On other hand, subtle structural difference between pseudoenantiomeric could also lead uneven efficiency that severely...
An efficient and practical protocol for the highly selective preparation of substituted allyl sulfones has been developed. Arenesulfonyl cyanides, Baylis–Hillman adducts, simple allylic alcohols give an unforeseen outcome (see scheme).
We describe the research that led to discovery of compound 40 (ruzasvir, MK-8408), a pan-genotypic HCV nonstructural protein 5A (NS5A) inhibitor with "flat" GT1 mutant profile. This NS5A contains unique tetracyclic indole core while maintaining imidazole-proline-valine Moc motifs our previous inhibitors. Compound is currently in early clinical trials and under evaluation as part an all-oral DAA regimen for treatment chronic infection.
Dimethyl succinate (DMS) is a key raw material for polybutylene (PBS) production, developing sustainable, low-cost processes and efficient heterogeneous catalysts hold significant economic value. Herein, we demonstrated that an...
Kilogram-scale syntheses of fragments C1-6 (6) and C9-14 (4) (+)-discodermolide from common precursor 3 are described. Improved procedures for each step both were developed by minimizing or eliminating the formation byproducts that isolated characterized in Smith's synthesis.
Gif chemistry permits the selective functionalization of saturated hydrocarbons under very mild conditions. The formation alkyl chlorides is shown to derive from an FeII–FeIV manifold and distinct usual ketonization process (Gif chemistry) produced by FeIII–FeV manifold. importance certain carboxylic acids such as picolinic acid 1 for hydrocarbon activation highlighted. ligand environment catalyst in solution clarified using 13C NMR spectroscopy. Evidence a µ-peroxo-dimer species key...
A highly diastereoselective addition of substituted racemic allylic zinc reagents to chiral N-tert-butanesulfinylimines resulting in the formation homoallylic amines is reported. This method quite general and also efficient for preparation enantiomerically pure bearing quaternary centers adjacent centers.
A planar chiral ferrocene derivative Fc-DHIPOH served as an excellent N,O- ligand for asymmetric copper catalyzed 1,4-addition of glycine derivatives to alkylidene malonates. The corresponding 1,4-adducts were obtained in high yields with enantioselectivities up 95% ee.
An efficient and practical N-methylation of amino acid derivatives with dimethyl sulfate in the presence sodium hydride a catalytic amount water is described. Reaction generated highly reactive dry hydroxide, which led to much faster reaction rates than powdered hydroxide itself.
Planar chiral nucleophilic catalyst Fc-PIP was employed in the kinetic resolution of bulky (hetero)arylalkyl carbinols delivering unreacted alcohols with extremely high enantiomeric excess (>99.0% ees) ideal conversions ranging from 50.4–56.7%.
A scale-up synthesis of antidepressant drug vilazodone was accomplished in five steps. Friedel–Crafts acylation 1-tosyl-1H-indole-5-carbonitrile with 4-chlorobutyryl chloride, selective deoxygenation NaBH4/CF3COOH system coupled ethyl 5-(piperazin-1-yl)-benzofuran-2-carboxylate hydrochloride, one-step deprotection and esterolysis, the final ammonolysis led to target molecule 52.4% overall yield 99.7% purity. This convenient economical procedure is remarkably applicable for production.
The discovery of potent and pan-genotypic HCV NS5A inhibitors faces many challenges including the significant diversity among genotypes, substantial potency shift conferred on some key resistance-associated variants, inconsistent SARs between different genotypes mutants, lacking models inhibitor/protein complexes for rational inhibitor design. As part ongoing efforts inhibition at Merck, we now describe a novel series chromane containing inhibitors. SAR studies around "Z" group tetracyclic...
Enabled by the discovery of new cinchonium salts and coadditives, a direct efficient asymmetric access to trifluoromethylated γ-amino esters/lactones has been realized through enantioselective diastereoselective umpolung reaction trifluoromethyl imines with acrylates or α,β-unsaturated lactones as carbon electrophiles. At 0.5–5.0 mol % catalyst loadings, newly developed catalytic system activates variety imine substrates unconventional nucleophiles mediate highly chemo-, regio-, diastereo-,...