Erythropoietin (EPO) may become a potential therapeutic candidate for the treatment of the neurodegenerative disorder -- Parkinson's disease (PD), since EPO has been found to prevent neuron apoptosis through the activation of cell survival signalling. However, the underlying mechanisms of how EPO exerts its neuroprotective effect are not fully elucidated. Here we investigated the mechanism by which EPO suppressed 6-hydroxydopamine (6-OHDA)-induced neuron death in in vitro and in vivo models of PD. EPO knockdown conferred 6-OHDA-induced cytotoxicity. This effect was reversed by EPO administration. Treatment of PC12 cells with EPO greatly diminished the toxicity induced by 6-OHDA in a dose- and time-dependent manner. EPO effectively reduced apoptosis of striatal neurons and induced a significant improvement on the neurological function score in the rat models of PD. Furthermore, EPO increased the expression of phosphorylated Akt and phosphorylated FoxO3a, and abrogated the 6-OHDA-induced dysregulation of Bcl-2, Bax and Caspase-3 in PC12 cells and in striatal neurons. Meanwhile, the EPO-dependent neuroprotection was notably reversed by pretreatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). Our data suggest that PI3K/Akt/FoxO3a signalling pathway may be a possible mechanism involved in the neuroprotective effect of EPO in PD.

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The restricted availability, expense and toxicity of precious metal catalysts such as rhodium and palladium challenge the sustainability of synthetic chemistry. As such, nickel catalysts have garnered increasing attention as replacements for enyne cyclization reactions. On the other hand, bridged tricyclo[5.2.1.0 1,5 ]decanes are found as core structures in many biologically active natural products; however, the synthesis of such frameworks with high functionalities from readily available precursors remains a significant challenge. Herein, we report a nickel-catalyzed asymmetric domino cyclization reaction of enynones, providing rapid and modular synthesis of bridged tricyclo[5.2.1.0 1,5 ]decane skeletons with three quaternary stereocenters in good yields and remarkable high levels of regio-and enantioselectivities (92-99% ee).

The reductive coupling of alkynes represents a powerful strategy for the rapid synthesis of highly substituted 1,3-dienes. This method has the advantages of high atom and step economy, easily available...

The introduction of fluorine‐containing groups into organic molecules can significantly affect their physical and chemical properties and has long been used as an effective strategy for drug discovery and development. Consequently, the development of catalytic asymmetric methods for the synthesis of fluorine‐containing heterocycles is highly desirable and sought after. Herein, we describe a nickel‐catalyzed defluorinative asymmetric cyclization of fluoroalkyl‐substituted 1,6‐enynes, providing an expedient access to synthetically attractive 4‐fluorovinyl‐substituted 2‐pyrrolidones in good yields with remarkable high levels of chemo‐, regio‐, and enantioselectivities (90–99 % ee,>35 examples). This protocol features readily available starting materials and excellent functional group compatibility, and exhibits complementary regioselectivity. The utility of this strategy was demonstrated in the enantioselective synthesis of the antiepileptic drug Seletracetam.