Stroke is a complex disease involved oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway has been considered a potential target for neuroprotection in stroke. Acetyl-11-Keto-β-Boswellic Acid (AKBA) is an active triterpenoid compound from the extract of Boswellia serrate. The present study was to determine whether AKBA, a novel Nrf2 activator, can protect against cerebral ischemic injury. The stroke model was produced in Sprague–Dawley rats via middle cerebral artery occlusion. To model ischemia-like conditions in vitro, primary cultured cortical neurons were exposed to transient oxygen and glucose deprivation (OGD). Treatment of AKBA significantly reduced infarct volumes and apoptotic cells, and also increased neurologic scores by elevating the Nrf2 and HO-1 expression in brain tissues in middle cerebral artery occlusion (MCAO) rats at 48 hours post reperfusion. In primary cultured neurons, AKBA increased the Nrf2 and HO-1 expression, which provided protection against OGD-induced oxidative insult. Additionally, AKBA treatment increased Nrf2 binding activity to antioxidant-response elements (ARE). The protective effect of AKBA was attenuated by knockdown of Nrf2 or HO-1. In conclusion, these findings provide evidence that AKBA protects neurons against ischemic injury, and this neuroprotective effect involves the Nrf2/HO-1 pathway.

The asymmetric construction of a stereogenic carbon center with four non-hydrogen substituents, that is, a quaternary carbon atom, represents one of the most challenging and demanding topics in the synthesis of natural products and chiral drugs.[1] The construction of quaternary carbon centers bearing a nitrogen atom, which is a fairly ubiquitous structure in natural alkaloids, [2] has drawn increasing attention and several catalytic asymmetric procedures have been successfully developed.[3] The catalytic asymmetric Friedel-Crafts reaction has attracted much attention over the past decades as a versatile C À C bond-forming process, and great progress has been reported.[4] However, to the best of our knowledge, no efficient method has been reported for the creation of a nitrogen-containing quaternary carbon center by using the asymmetric Friedel-Crafts reaction.[5] Herein, we describe an enantioselective Friedel-Crafts reaction of indoles (2) with aaryl enamides 3 catalyzed by chiral Brønsted acids 1[6] to provide chiral tertiary amines 4 with a quaternary carbon center in excellent yields and high enantioselectivities (Scheme 1). [7] It is noteworthy that while the enamides have generally been used as nucleophiles in acid-catalyzed reactions, [8] the a-aryl enamides 3 have played the role of the electrophile in the reaction with indoles. [9] The initial reaction of indole (2 a) and a-phenyl enamide (3 a) was performed at room temperature in dichloromethane in the presence of 10 mol % of the chiral binol-based phosphoric acid 1 a as the catalyst (binol = 2,2'-dihydroxy-1,1'-binaphthyl). The Friedel-Crafts product, N-(1-(3-indolyl)-1-phenylethyl)acetamide (4 aa) was obtained in 74 % yield but with almost no enantioselectivity (Table 1, entry 1). We then concentrated on the modification of the structure of the chiral phosphoric acid catalyst. A series of chiral phosphoric acids 1 with different substituents at the 3,3'-positions of the binaphthyl ring were prepared and tested in the reaction of indole (2 a) and a-phenyl enamide (3 a). The sterically congested phosphoric acid catalysts were found to be crucial for achieving high enantioselectivity, with the catalyst 1 j bearing bulky 2,4,6-triisopropylphenyl groups at Scheme 1. Asymmetric Friedel-Crafts reaction of indole (2 a) and N-(1-phenylvinyl)acetamide (3 a) catalyzed by a chiral Brønsted acid. ee [%][c]

Bring on the big cats: New, C2-symmetric bulky N-heterocyclic carbene ligands bring major improvements in the palladium-catalyzed asymmetric intramolecular α-arylation of amides to give oxindoles (see picture, dba=trans,trans-dibenzylideneacetone), which are formed in high yield and excellent enantiomeric purity

A highly enantioselective intramolecular arylative dearomatization of indoles via palladium-catalyzed reductive Heck reactions was developed. The new strategy led to a series of optically active indolines bearing C2-quaternary stereocenters in modest to good yields with excellent enantioselectivities (up to 99% ee).

As a biomarker for early cancer diagnosis, telomerase are one of the promising targets for cancer therapeutics. Inspired by the fluorescent emission principle of aggregation-induced emission fluorogens, we creatively designed an AIE-based turn-on method to detect telomerase activity from cell extracts. A positively charged fluorogen (TPE-Z) is not fluorescent when freely diffused in solution. The fluorescence of TPE-Z is enhanced with the elongation of the DNA strand which could light up telomere elongation process. By exploitation of it, we can detect telomerase activity from different cell lines (E-J, HeLa, MCF-7, and HLF) with high sensitivity and specificity. Moreover, our method is successfully employed to demonstrate the applications in bladder cancer diagnosis (41 urine specimens from bladder cancer patients and 15 urine specimens from normal people are detected). The AIE-based method provides a simple one-pot technique for quantification and monitoring of the telomerase activity and shows great potential for future use in clinical tests.

[reaction: see text] A novel asymmetric Friedel-Crafts alkylation of indoles with nitroalkenes catalyzed by Zn(II)-bisoxazoline complexes has been developed. The nitroalkylated indoles are synthesized in excellent yields and high enantioselectivities (up to 90% ee). The effects of ligand structure, metal salt, and solvent on the reaction are discussed. The substrates of the reaction can be aromatic, heteroaromatic, and even aliphatic nitroalkenes. The high reactivity and selectivity of the reaction are presumptively attributed to the activation and asymmetric induction of chiral Lewis acids coordinated by nitroalkene substrates through a 1,3-metal bonding model.

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An efficient process based on the gold-catalyzed redox reaction has been developed to oxidize 1,2-diarylacetylene or ynamide to 1,2-diaryldiketone or α-keto imide respectively. This process can tolerate a variety of functional groups and affords 1,2-dicarbonyl compounds in excellent yields under mild reaction conditions.