Xiao Ding

Gold-catalyzed intramolecular hydroamination of terminal alkynes in aqueous media: efficient and regioselective synthesis of indole-1-carboxamides

Using [Au(PPh3)]Cl/Ag2CO3-catalyzed 5-endo-digcyclization in water under microwave irradiation, we developed a fast and green route to prepare indole-1-carboxamides from N′-substituted N-(2-alkynylphenyl)ureas. The described method is tolerant to a variety of functional groups, including N′-aryl, alkyl, heterocyclic, various N-(substituted-2-ethynylphenyl) and N-(2-ethynylpyridin-3-yl)ureas and affords moderate to high yields of the desired products.

Asymmetric Synthesis of Sterically and Electronically Demanding Linear ω-Trifluoromethyl Containing Amino Acids via Alkylation of Chiral Equivalents of Nucleophilic Glycine and Alanine

An operationally convenient, scalable asymmetric synthesis of linear, ω-trifluoromethyl-containing amino acids, which were not previously produced in their enantiomerically pure form, has been developed via alkylation of chiral equivalents of nucleophilic glycine and alanine. The simplicity of the experimental procedures and high stereochemical outcome (yields up to 90% and diastereoselectivity up to 99%) of the presented method render these fluorinated amino acids readily available for systematic medicinal chemistry studies and de novo peptide design.

Design, synthesis, and interaction study of quinazoline-2(1H)-thione derivatives as novel potential Bcl-xL inhibitors.

Development of inhibitors to antagonize the activities of antiapoptotic Bcl-2 family proteins is of particular interest in cancer chemotherapy. We discovered a quinazoline-2(1H)-thione derivative (DCBL55) as a new Bcl-x(L), Bcl-2, and Mcl-1 inhibitor by virtual database screening. We systematically modified the structure of compound 1 by chemical synthesis. The interactions of the compounds with Bcl-x(L) were predicted by molecular modeling simulations, which were confirmed by structure-activity relationship analysis and protein mutation studies. Three locations at the hydrophobic groove of Bcl-x(L), referred to as P2, P4, and P5, were found to contribute to the ligand interactions. Although the compounds induced mitochondrial potential reduction, caspase activation, and ROS generation, the cytotoxicities and the ultrastructural changes of outer mitochondrial membrane suggested that the compounds may target additional proteins outside the Bcl-2 family. Altogether, the present study provides new lead compounds and critical structural information for further development of more potent and specific inhibitors of antiapoptotic Bcl-2 family proteins.

Silver- and Gold-Mediated Intramolecular Cyclization to Substituted Tetracyclic Isoquinolizinium Hexafluorostilbates

A convenient route for the synthesis of various charged tetracyclic isoquinolizinium hexafluorostilbates was developed using AgSbF(6)/AuCl(PPh(3)) for the intramolecular addition of amine to alkyne. The described process is tolerant of a variety of functional groups and broadens the diversity of substrates with the use of 8-substituted tetracyclic isoquinolizinium salts.

Efficient Synthesis of α-Aryl-/Heteroaryl-Substituted β-Amino Acids via Ni(II) Complex through the Suzuki Coupling Reaction

We described a synthesis method by first using chlorotrimethylsilane as the activator to brominate the Ni(II) complex of the beta-alanine Schiffs base [beta-AlaNi(II)PABA] 1 and developed it to prepare beta-amino acids 5. The procedure involves a Suzuki coupling reaction between boric acids and the bromoenone 2, followed by hydrogenation and hydrolysis. This is the first report of the application of the Ni (II) complex [beta-AlaNi(II)PABA], which represents an attractive route to afford alpha-aryl-/heteroaryl-substituted beta-amino acids.

Efficient Synthesis of Symmetrical α,α-Disubstituted β-Amino Acids and α,α-Disubstituted Aldehydes via Dialkylation of Nucleophilic β-Alanine Equivalent

Homologation of the nucleophilic beta-alanine equivalent beta-Ala Ni(II)-PABP [Ni(II) complex of beta-alanine Schiff base with 2-[N-(alpha-picolyl)amino]benzophenone (PABP), 1] via alkyl halide alkylation was systematically studied as a general method for preparing symmetrically alpha,alpha-disubstituted beta-amino acids. The dialkylation reactions could be easily performed and did not require inert atmosphere, dried solvents, and low temperatures, thereby affording the benefits of operationally convenient experimental procedure and high atom economy. Further, the methodology developed by us can also be used to generate symmetrical alpha,alpha-disubstituted aldehydes through an alternative decomposition method.

Anthraquinone Derivatives as Potent Inhibitors of c-Met Kinase and the Extracellular Signaling Pathway

The aberrant function of c-Met kinase signaling pathway is ubiquitously involved in a broad spectrum of human cancers; thus, a strong rationale exists for targeting the kinase pathway in cancer therapy. Via integration of computational and experimental studies, anthraquinone derivatives were identified for the first time as potent c-Met kinase inhibitors in this research. The aberrant activation of the c-Met kinase pathway results from (TPR)-Met, MET gene mutation, or amplification and a hepatocyte growth factor (HGF)/scatter factor-dependent autocrine or paracrine mechanism. However, anthraquinone derivatives exclusively suppressed c-Met phosphorylation stimulated by HGF in A549 cells, indicating that the compounds possess the ability to block the extracellular HGF-dependent pathway. A surface plasmon resonance assay revealed that the most potent compound, 2a, shows a high binding affinity for HGF with an equilibrium dissociation constant of 1.95 μM. The dual roles of compound 2a demonstrate the potency of anthraquinone derivatives and provide a new design solution for the c-Met kinase signaling pathway.

Preparation of α-alkyl-β-amino acids via β-alanine Ni(II) complex.

A new β-amino acrylic acid Ni(II) complex has been developed and used for the synthesis of α-alkyl-β-amino acids via alkylation with alkyl halides under operationally convenient conditions. The pivotal α-alkylated intermediate can be converted into the corresponding α-alkyl-β-amino acids via two steps with a wide range of substituents.

Synthesis of 2-Phenylnaphthalenes Through Gold-Catalyzed Dimerization via a Highly Selective Carbon Nucleophile Pathway.

A protocol for the facile synthesis of 2-phenylnaphthalene has been developed. The benzyl carbon acts as a nucleophilic center in the presence of the amide nitrogen and acetate oxygen, affording the selective formation of a naphthalene scaffold through the dimerization of the reactants.

Correction to Anthraquinone Derivatives as Potent Inhibitors of c-Met Kinase and the Extracellular Signaling Pathway.

[This corrects the article DOI: 10.1021/ml4000047.].