RESUMEN
Amides are one of the most important organic compounds that are widely applied in medicine, biochemistry, and materials science. To find an efficient synthetic method of amides is a challenge for organic chemistry. We report here a facile synthesis method of primary and secondary amides through a direct amidation of esters with sodium amidoboranes (NaNHRBH3, R = H, Me), at room temperature without using catalysts and other reagents. This process is rapid and chemoselective, and features quantitative conversion and wide applicability for esters tolerating different functional groups. The experimental and theoretical studies reveal a reaction mechanism with nucleophilic addition followed by a swift proton transfer-induced elimination reaction.
RESUMEN
OBJECTIVE: To investigate the effects of Deoxygedunin on Aß deposition, learning memory, and oxidative stress induced by D-galactose combined with AlCl3 in model rats with Alzheimer's disease and its possible mechanism. METHODS: Male SD rats were randomly divided into three groups (n=12):control group, model group (AD) and intervention group (AD+Deo). Morris water maze test was used to detect learning/memory and cognitive function in rats.Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) contents in homogenate of hippocampus were detected by enzyme-linked immunosorbent assay (ELISA).Tau protein expression in rat cerebral cortex was detected by immunohistochemistry.Western blot was used to detect the expressions of extracellular signal regulated kinase 1(ERK1), protein kinase B (PKB) and tropomyosin-related kinase B (TrkB) on TrkB signaling pathway. RESULTS: The results of water maze test showed that D-galactose combined with AlCl3 induced a significant increase in the escape latency compared with the control group (P<0.05).Deoxygedunin could reverse the increase of the escape latency of the model group (P<0.05).On the 7th day after removal of the platform, the model group showed an increase in escape latency compared with the control group and the intervention group (P<0.01), and the number of crossing platforms was declined (P<0.05); The results of immunohistochemistry and ELISA showed that the expressions of Aß and tau protein in the model group were increased significantly compared with those of the control group (P<0.01).The activities of SOD and GSH-Px were decreased significantly and the content of MDA was increased significantly.Compared with the model group, Deoxygedunin could reverse the increase of the expressions of Aß and tau protein (P<0.01), the decrease of SOD and GSH-Px activities (P<0.05) and the increase of the MDA content (P<0.05).Western blot results showed that Deoxygedunin treatment reversed the decreased phosphorylation levels of TrkB, AKT and ERK1 in hippocampus of the model group. CONCLUSIONS: Supplement of Deoxygedunin can significantly reverse Aß deposition, oxidative stress and cognitive deficits by activating the TrkB signal transduction pathway, which suggest that Deoxygedunin may serve as a promising therapeutic candidate for attenuating AD-like pathological dysfunction induced by D-galactose combined with AlCl3.