Palladium catalyzed cascade umpolung allylation/acetalation for the construction of quaternary 3-amino oxindoles.

Herein we reported a highly diastereoselective synthesis of quaternary 3-amino oxindoles bearing an acetal unit via a palladium catalyzed three-component cascade umpolung allylation/acetalation process. An array of 3-amino 3-allyl oxindoles incorporating diversified functional groups were prepared in good yields with exclusive diastereoselectivities. Further investigation demonstrated that the current method could also be extended to cascade umpolung allenylation/acetalation.

Catalytic Asymmetric Synthesis of α-Trifluoromethyl Homoallylic Amines via Umpolung Allylation/2-Aza-Cope Rearrangement: Stereoselectivity and Mechanistic Insight.

An unprecedented Ir-catalyzed asymmetric cascade umpolung allylation/2-aza-Cope rearrangement of trifluoroethylisatin ketimines has been realized. The current method provides a facile access to biologically important α-trifluoromethyl-containing homoallylic amines in high yields with excellent enantioselectivity. Notably, umpolung reactivity of trifluoroethylisatin ketimine was discovered for the first time. Mechanism studies revealed the key intermediates in the initial umpolung allylation and the stereospecific chirality transfer in the subsequent 2-aza-Cope rearrangement.

Catalytic Asymmetric Desymmetrization of Cyclopentendiones via Diels-Alder Reaction of 3-Hydroxy-2-pyrones: Construction of Multifunctional Bridged Tricyclic Lactones.

An unprecedented asymmetric Diels-Alder reaction of 3-hydroxy-2-pyrones with prochiral cyclopentene-1,3-diones via desymmetrization was efficiently realized with high stereoselective control with the aid of fine-tunable cinchona alkaloid derived bifunctional amine-thiourea catalysts bearing multiple hydrogen-bonding donors. This protocol provides an expedient access to the multifunctional-bridged tricyclic lactones featuring four contiguous stereogenic centers and one remote quaternary stereogenic center with a broad substrate scope. The cycloadduct can be readily elaborated into enantioenriched cyclopentane-1,3-diones via ring opening/aromatization.

Molecular Diversity of Sapovirus Infection in Outpatients Living in Nanjing, China (2011-2013).

Aim. To gain insight into the molecular diversity of sapovirus in outpatients with acute gastroenteritis in Nanjing, China. Methods. The specimens from outpatients clinically diagnosed as acute gastroenteritis were detected by real-time PCR; RT-PCR was then performed to amplify part of VP1 sequences. The PCR products were cloned into pGEM-T Easy vector and bidirectionally sequenced. All sequences were edited and analyzed. A phylogenetic tree was drawn with the MEGA 5.0 software. Results. Between 2011 and 2013, 16 sapovirus positive cases were confirmed by real-time PCR. The infected cases increased from two in 2011 and six in 2012 to eight in 2013. The majority was children and the elderly (15, 93.75%) and single infections (15, 93.75%). Of the 16 real-time positive specimens, 14 specimens had PCR products and the analysis data of the 14 nucleic sequences showed that there was one GI genogroup with four genotypes, two GI.2 in 2011, three GI.2, and one GI.1 in 2012 and one GI.2, three GI.1, two GI.3, and two GI.5 in 2013. Conclusion. Our data confirmed continuous existing of GI genogroup and GI.2 genotype from 2011 to 2013 in Nanjing and the successive appearance of different genotypes from outpatients with gastroenteritis.

6-Hydroxydopamine promotes iron traffic in primary cultured astrocytes.

It is well known that disrupted brain iron homeostasis was involved in Parkinson's disease. We previously reported 6-hydroxydopamine (6-OHDA) could enhance iron influx and attenuate iron efflux process, thus promote iron accumulation in neurons. Astrocytes, the major glial cell type in the central nervous system, are largely responsible for iron distribution in the brain. However, how iron metabolism changes in astrocytes with 6-OHDA treatment are not fully elucidated. In the present study, we first observed that both iron influx and efflux were enhanced with 10 µM 6-OHDA treatment for 24 h in primary cultured astrocytes. In accordance with these iron traffic modulations, both mRNA and protein levels of iron importer divalent metal transporter 1 with iron responsive element (DMT1+IRE) and exporter ferroportin 1 (FPN1) were up-regulated in these cells. L-ferritin mRNA levels were increased. Iron regulatory protein 1 (IRP1) showed a dynamic regulation with 6-OHDA treatment, as indicated by a moderate up-regulation at 12 h, however, down-regulation at 24 h. We further demonstrated that 6-OHDA treatment could induce activation of nuclear factor-kappaB (NF-κB) p65. IκBα activation inhibitor BAY11-7082 fully blocked 6-OHDA induced NF-κB p65 phosphorylation and DMT1 + IRE up-regulation. These results suggest that 6-OHDA might promote iron transport rate in astrocytes by regulating iron transporters, IRP1 expression and NF-κB p65 activation, indicating a different response between neurons and astrocytes.

Postnatal development in Andersen's leaf-nosed bat Hipposideros pomona: flight, wing shape, and wing bone lengths.

Postnatal changes in flight development, wing shape and wing bone lengths of 56 marked neonate Hipposideros pomona were investigated under natural conditions in southwest China. Flight experiments showed that pups began to flutter with a short horizontal displacement at 10 days and first took flight at 19 days, with most achieving sustained flight at 1 month old. Analysis of covariance on wingspan, wing area, and the other seven wing characteristics between 'pre-flight' and 'post-volancy' periods supports the hypothesis that growth had one 'pre-flight' trajectory and a different 'post-volancy' trajectory in bats. Wingspan, handwing length and area, armwing length and area, and total wing area increased linearly until the age of first flight, after which the growth rates decreased (all P < 0.001). Wing loading declined linearly until day 19 before ultimately decreasing to adult levels (P < 0.001). Additionally, the relationship of different pairwise combinations of bony components composing span-wise length and chord-wise length was evaluated to test the hypothesis that compensatory growth of wing bones in H. pomona occurred in both 'pre-flight' and 'post-volancy' periods. The frequency of short-long and long-short pairs was significantly greater than that of short-short, long-long pairs in most pairs of bone elements in adults. The results indicate that a bone 'shorter than expected' would be compensated by a bone or bones 'longer than expected', suggesting compensatory growth in H. pomona. The pairwise comparisons conducted in adults were also performed in young bats during 'pre-flight' and 'post-volancy' periods, demonstrating that compensatory growth occurred throughout postnatal ontogeny.

Mitochondria dysfunction was involved in copper-induced toxicity in MES23.5 cells.

OBJECTIVE: To investigate the toxicity of copper on MES23.5 dopaminergic cells and the probable mechanisms involved in this process. METHODS: MES23.5 dopaminergic cells were selected as our experimental model. [3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide] (MTT) assay was used to detect the influence of copper on the cell viability. The semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), Western blotting and the high performance liquid chromatography-electrochemical detection (HPLC-ECD) have been used to detect the tyrosine hydroxlase (TH) mRNA and protein expression and the dopamine content in MES23.5 cells. The flow cytometry have been used to detect the changes of mitochondrial transmembrane potential. RESULTS: 100 and 200 mumol/L copper had no effect on the MES23.5 cell viability, whereas 400 and 800 mumol/L of copper could decrease the cell viability (P < 0.01). Treating cells with 200 mumol/L copper for 24 h decreased the TH mRNA expression, the TH expression and the dopamine content compared with the control (P < 0.01, P < 0.01, P < 0.05, respectively). Besides, the mitochondrial transmembrane potential also decreased with the treatment of 200 mumol/L copper for 24 h (P < 0.01). CONCLUSION: Copper could exert the toxic effects on MES23.5 dopaminergic cells and decrease the cell function. The dysfunction of mitochondria may be the mechanism of this toxicity effect.