Recent advances in transition-metal-catalysed asymmetric coupling reactions with light intervention.

Transition metal-catalysed asymmetric coupling has been established as a robust tool for constructing complex organic molecules. Although this area has been extensively studied, the development of efficient protocols to construct stereogenic centres with excellent regio- and enantioselectivities is highly desirable and remains challenging. Asymmetric transition metal catalysis with light intervention provides a practical alternative strategy to current methods and considerably expands the synthetic utility as a result of abundant feedstocks and mild conditions. This tutorial review comprehensively summarizes the recent advances in transition-metal-catalysed asymmetric coupling reactions with light intervention; in particular, a concise analysis of substrate scope and the mechanistic scenarios governing stereocontrol is discussed.

Enantioselective Radical Carbocyanation of 1,3-Dienes via Photocatalytic Generation of Allylcopper Complexes.

1,3-Dienes are readily available feedstocks that are widely used in the laboratory and industry. However, the potential of converting 1,3-dienes into value-added products, especially chiral products, has not yet been fully exploited. By synergetic photoredox/copper catalysis, we achieve the first visible-light-induced, enantioselective carbocyanation of 1,3-dienes by using carboxylic acid derivatives and trimethylsilyl cyanide. Under mild and neutral conditions, a diverse range of chiral allyl cyanides are produced in generally good efficiency and with high enantioselectivity from bench-stable and user-safe chemicals. Moreover, preliminary results also confirm that this success can be expanded to 1,3-enynes and the four-component carbonylative carbocyanation of 1,3-dienes and 1,3-enynes.

Visible-light-induced triple catalysis for a ring-opening cyanation of cyclopropyl ketones.

An unprecedented triple catalytic, general ring-opening cyanation reaction of cyclopropyl ketones for the construction of γ-cyanoketones is described. The key is to merge photoredox catalysis with Lewis acid catalysis and copper catalysis to enable the selective cleavage of the carbon-carbon bonds and the selective coupling of the generated radical and cyanide anion.

Exploration of a Chiral Cobalt Catalyst for Visible-Light-Induced Enantioselective Radical Conjugate Addition.

Chiral catalysts tolerating photochemical reactions are in great demand for the vast development of visible-light-induced asymmetric synthesis. Now, chiral octahedral complexes based on earth-abundant metal and chiral N4 ligands are reported. One well-defined chiral CoII -complex is shown to be an efficient catalyst in the visible-light-induced conjugated addition of enones by alkyl and acyl radicals, providing synthetically valued chiral ketones and 1,4-dicarbonyls in 47->99 % yields with up to 97:3 e.r.

Asymmetric Propargylic Radical Cyanation Enabled by Dual Organophotoredox and Copper Catalysis.

The first asymmetric propargylic radical cyanation was realized through a dual photoredox and copper catalysis. An organic photocatalyst serves to both generate propargyl radicals and oxidize Cu(I) species to Cu(II) species. A chiral Cu complex functions as an efficient organometallic catalyst to resemble the propargyl radical and cyanide in an enantio-controlled manner. Thus, a diverse range of optically active propargyl cyanides were produced with high reaction efficiency and enantioselectivities (28 examples, 57-97% yields and 83-98% ee). Moreover, mechanistic investigations including experiments and density functional theory calculations were performed to illustrate on the reaction pathway and stereochemical results.

[The effect of 5-fluorouracil on enriching cancer stem cells of hepatoma cell line BEL-7402].

OBJECTIVE: To investigate the effect of 5-FU (5-fluorouracil) on enriching cancer stem cells of HCC cell line BEL-7402 and the biological characteristics of enriched cells. METHODS: The enriching concentration of 5-FU was determined by CCK-8 (cell counting kit-8). Flow Cytometry was used to determine the changes in cell cycle and positive expression ratio of surface marker CD56, CD54, EpCAM and CD133. The self-renewal and differentiation of positive cells were tested by colony formation assay, and were compared with the control group. RESULTS: Enriching concentration of 5-FU was determined as 10 µg/ml with 48 h incubation. After enrichment, G0/G1 phase cells increased from 57.50 %+/-0.98% to 68.70%+/-3.41% (P<0.05). Whereas S phase cells decreased from 40.26%+/-4.12% to 31.80%+/-4.15% (P<0.01); G2/M phase cells disappeared in experimental group, and was 5.80%+/-1.87% in control group (P<0.01). The proportion of the cell cycle changed with significant statistical differences. Meanwhile, positive rate of cell surface makers CD56, CD54, EpCAM and CD133 increased from 0.57%+/-0.12%, 8.10%+/-6.79%, 0.3%+/-0.01% and 3.20%+/-0.99% to 4.13%+/-0.06%, 50.08%+/-1.69%, 0.55%+/-0.07% and 10.51%+/-1.13%, respectively. The difference was significant (P<0.05). The colony forming ratio of CD56, CD54, EpCAM and CD133 negative cells and positive cells were 2.11%+/-0.21%, 3.32%+/-0.31%; 0.86%+/-0.101%, 2.40%+/-0.52 %; 7.19%+/-0.56%, 7.73%+/-0.71%; 2.70%+/-0.26%, 5.75%+/-0.81%, respectively, and significant differences were found between (P<0.05). CONCLUSION: 5-fluorouracil enriched the cancer stem cell population in HCC cell line BEL-7402. CD56 and CD54 can be used as important surface markers in research of liver cancer stem cells.

[Pulmonary pathology in fatal human influenza A (H1N1) infection].

OBJECTIVE: To study the pulmonary pathology in patients died of fatal human influenza A(H1N1) infection. METHODS: Eight cases of fatal human influenza A (H1N1) infection, including 2 autopsy cases and 6 paramortem needle puncture biopsies, were enrolled into the study. Histologic examination, immunohistochemitry, flow cytometry and Western blotting were carried out. RESULTS: The major pathologic changes included necrotizing bronchiolitis with surrounding inflammation, diffuse alveolar damage and pulmonary hemorrhage. Influenza viral antigen expression was detected in the lung tissue by Western blotting. Immunohistochemical study demonstrated the presence of nuclear protein and hemagglutinin virus antigens in parts of trachea, bronchial epithelium and glands, alveolar epithelium, macrophages and endothelium. Flow cytometry showed that the apoptotic rate of type II pneumocytes (32.15%, 78.15%) was significantly higher than that of the controls (1.93%, 3.77%). CONCLUSION: Necrotizing bronchiolitis, diffuse alveolar damage and pulmonary hemorrhage followed by pulmonary fibrosis in late stage are the major pathologic changes in fatal human influenza A (H1N1) infection.

[Experimental research of discordant tracheal xenotransplantation].

OBJECTIVE: To investigate the immunological rejection mechanism of tracheal xenotransplantation and xenografts as potential sources of trachea. METHODS: On SD rat model, a xenotransplanted tracheal from the guinea pig was established by wrapping it in the cervical muscles in situ. It was divided into cryopreserved group and uncryopreserved group. Under the examinations with histochemistry, immunofluorescence (IFL) and flow cytometry (FCM) techniques, the pathomorphological characteristics of the tracheal xenografts and the immunological rejection mechanism were evaluated. RESULTS: The tracheal allotransplantation with cryopreserved grafts wrapped by neck muscles was survived for a longer period. Histological examination revealed normal appearance of the allografts. The tracheal grafts patency was above 80%. However, cryopreserved tracheal xenografts of the guinea pig-to-rat maintained vitality for 14 days in maximum and 13.2 days on average, while the fresh tracheal xenografts only for 9 days in maximum, and 8 days on average. Acute rejection occurred in the tracheal xenotransplantation. A marked mononuclear-macrophage cellular infiltration mixed with eosinophils and lymphocyte was seen in the xenografts. Antibody (IgM, IgG) and complement (C3) deposition were also obviously detected by IFL in the xenografts. CD4 T+ cells and CD8+ T cells increased significantly in the vascular circulation. In all of the xenografts, complete loss of tracheal epithelium was associated with cartilage necrosis. The grafts patency was below 50%. This performance deteriorated with extended time periods. The fresh xenografts performed significantly worse than the cryopreserved xenografts. CONCLUSIONS: Acute rejection, caused by humoral immune reaction mainly integrated with cellular immunity, is the most notable characteristics in the guinea pig-to-rat tracheal xenotransplantation in situ. Cryopreservation can potentially reduce the antigenicity. The low antigenicity may inhibit the immunologic reaction relatively, so that prolonged survival of discordant cryopreserved tracheal xenografts could be achieved.