Dan Zhao

Iron-catalyzed oxidative synthesis of N-heterocycles from primary alcohols

An iron-catalyzed one-pot one-step oxidative system has been successfully developed in the conversion of primary alcohols into nitrogen-containing heterocycles, such as quinazolinone, quinazoline and 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide derivatives.

Ultrasound-promoted intramolecular direct arylation in a capillary flow microreactor.

An intramolecular direct arylation of various aryl bromides was performed using ultrasonic irradiation and a continuous flow capillary microreactor. The present procedure provided a higher functional group tolerance, ligand-free, milder reaction conditions and a shorter reaction time for the direct arylation compared with the conventional methods. The ultrasonic irritation not only greatly promoted the conversion and selectivity of the direct arylation, but also solved the clogging problem of the microreactor for solid-forming reaction and made the reaction run smoothly.

Metabonomic classification and detection of small molecule biomarkers of malignant pleural effusions

AbstractTo date, most research has been focused on the benign molecules in pleural effusions, and diagnosis of malignant ones still remains challenging. In the present study, targeting the small molecules as potential biomarkers to predict the malignancy of the effusions, the metabolic profiles of 81 clinical pleural effusions (41 malignant effusions from lung cancer and 40 benign ones) were investigated through a NMR-based metabonomic approach. In 1H NMR analysis, a total of ten small molecules in the effusions were simultaneously determined. Significantly higher mean values of valine, lactate, and alanine and markedly lower signal intensities of acetoacetate, trimethylamine-N-oxide, and α- and β-glucose were observed in malignant pleural effusions compared with those in benign ones. DFA modeling of NMR spectra subjected to a validation allowed the malignant effusions to be discriminated from benign ones in both training and validation groups. Currently, the conventional clinical analyses on chemical constituents in effusions could not provide a reliable prediction of malignancy of the effusions; the present results revealed that the small molecules might serve as useful biomarkers for diagnosis of the effusions, and the present NMR-based metabonomic approach provided a valuable potential to rapidly and sensitively predict the malignancy of the pleural effusions.n FigureNMR based metabonomic analysis of pleural effusions and diagnostic results with discriminant function analysis

Copper(II)-catalyzed C–H (sp3) oxidation and C–N cleavage: synthesis of methylene-bridged compounds using TMEDA as a carbon source in water

A green, simple, and efficient protocol for the selective methylenation via CuCl2/oxygen-mediated C–H (sp3) oxidation and C–N cleavage using tetramethylethylenediamine (TMEDA) as a carbon source has been developed. The reactions were achieved in green solvent water under atmospheric conditions. The protocol exhibited a broad substrate scope including indoles, anilines, pyrroles and 1,3-dicarbonyls. Furthermore, two key intermediates of the reaction were successfully identified and the mechanism was explored.

Ultrasound-promoted synthesis and immunosuppressive activity of novel quinazoline derivatives.

An environmentally friendly and mild Bischler cyclization was developed to access quinazolines with diverse substitution. Based on this method, a library of 53 quinazoline derivatives was prepared and tested in vitro for cytotoxicity and inhibition on T-cell and B-cell proliferation. Compounds 6b, 7b, 17b, 33, and 35 showed higher inhibitory activity on both T-cell and B-cell proliferations, with IC50 values of 6.16, 6.30, 5.43, 2.54, and 9.80xa0μM on T-cell, respectively. All the tested compounds showed no obvious cytotoxicity at 10xa0μM concentration. The preliminary structure–activity relationship was concluded revealing that 4-position is the key modification site for potent quinazoline immunosuppressive agent.

Neochromine S5 improves contact hypersensitivity through a selective effect on activated T lymphocytes

Strategy on activated T cells is an effective treatment for T cell mediated diseases. By using a synthesized chromone derivative, we examined its effects on the activated T cells. This compound, (Z)-1,3-dihydroxy-9-methyl-13H-benzo[b]chromeno[3,2-f][1,4]oxazepin-13-one (neochromine S5), exhibited immunosuppressive activity in vitro and in vivo. Interestingly, neochromine S5 selectively inhibited proliferation and induced apoptosis in T lymphocytes activated by concanavalin A (Con A) in a dose-dependent manner but not in naïve T lymphocytes, distinct from quercetin. This compound triggered mitochondrial apoptotic pathway including cleavage of caspase 3, caspase 9 and PARP, downregulation of bcl-2 and release of cytochrome c in activated T cells, but did not affect ER stress or Fas signals. In addition, neochromine S5 downregulated the expression of CD25 and CD69 and the production of inflammatory cytokines, including TNFα, IFNγ and IL-2, improved ear swelling in mice with contact hypersensitivity, reduced CD4(+) T cells infiltration, and increased apoptosis of isolated T lymphocytes from peripheral lymph nodes. Moreover, neochromine S5 showed no effect on the weight of mice and their immune organs, while dexamethasone caused a significant weight loss. Taken together, our results suggest that neochromine S5 exerts a unique anti-inflammatory activity mainly through a selective effect on activated T cells, which is different from the current immunosuppressant, dexamethasone.

Fluorescent Probes for Subcellular Localization during Osteclast Formation.

Labeling of a small bioactive molecule with fluorescent probe has been becoming an essential tool in cell biology to reveal the subcellular distribution and the location of a molecular target. QOA-8a is a novel molecule with potent antiosteoporotic effect in vivo. To investigate the molecular mechanism of QOA-8a, novel fluorescence-tagged chemical probes as bioactive as their parent molecule were designed and synthesized. The fluorescent compound 12 showed a more potent inhibitory activity on RANKL-induced osteoclastogenesis at 2 μM compared with that of QOA-8a. Microscopy experiments revealed that almost all of probe 12 accumulated in the fusing region, with little in the osteoclast precursors or the mature osteoclasts during osteoclast formation. The result suggests the location of the binding target of QOA-8a, which might greatly narrow down the search field of the target protein(s).