Electrooxidative Rhodium(III)/Chiral Carboxylic Acid-Catalyzed Enantioselective C-H Annulation of Sulfoximines with Alkynes.

The combination of achiral Cp*Rh(III) with chiral carboxylic acids (CCAs) represents an efficient catalytic system in transition metal-catalyzed enantioselective C-H activation. However, this hybrid catalysis is limited to redox-neutral C-H activation reactions and the adopt to oxidative enantioselective C-H activation remains elusive and pose a significant challenge. Herein, we describe the development of an electrochemical Cp*Rh(III)-catalyzed enantioselective C-H annulation of sulfoximines with alkynes enabled by chiral carboxylic acid (CCA) in an operationally friendly undivided cell at room temperature. A broad range of enantioenriched 1,2-benzothiazines are obtained in high yields with excellent enantioselectivities (up to 99 % yield and 98 : 2 er). The practicality of this method is demonstrated by scale-up reaction in a batch reactor with external circulation. A crucial chiral Cp*Rh(III) intermediate is isolated, characterized, and transformed, providing rational support for a Rh(III)/Rh(I) electrocatalytic cycle.

Ion Channels Involved in Substance P-Mediated Nociception and Antinociception.

Substance P (SP), an 11-amino-acid neuropeptide, has long been considered an effector of pain. However, accumulating studies have proposed a paradoxical role of SP in anti-nociception. Here, we review studies of SP-mediated nociception and anti-nociception in terms of peptide features, SP-modulated ion channels, and differential effector systems underlying neurokinin 1 receptors (NK1Rs) in differential cell types to elucidate the effect of SP and further our understanding of SP in anti-nociception. Most importantly, understanding the anti-nociceptive SP-NK1R pathway would provide new insights for analgesic drug development.

Acid-sensing ion channels: dual function proteins for chemo-sensing and mechano-sensing.

BACKGROUND: Acid-sensing ion channels (ASICs) are a group of amiloride-sensitive ligand-gated ion channels belonging to the family of degenerin/epithelial sodium channels. ASICs are predominantly expressed in both the peripheral and central nervous system and have been characterized as potent proton sensors to detect extracellular acidification in the periphery and brain. MAIN BODY: Here we review the recent studies focusing on the physiological roles of ASICs in the nervous system. As the major acid-sensing membrane proteins in the nervous system, ASICs detect tissue acidosis occurring at tissue injury, inflammation, ischemia, stroke, and tumors as well as fatiguing muscle to activate pain-sensing nerves in the periphery and transmit pain signals to the brain. Arachidonic acid and lysophosphocholine have been identified as endogenous non-proton ligands activating ASICs in a neutral pH environment. On the other hand, ASICs are found involved in the tether model mechanotransduction, in which the extracellular matrix and cytoplasmic cytoskeletons act like a gating-spring to tether the mechanically activated ion channels and thus transmit the stimulus force to the channels. Accordingly, accumulating evidence has shown ASICs play important roles in mechanotransduction of proprioceptors, mechanoreceptors and nociceptors to monitor the homoeostatic status of muscle contraction, blood volume, and blood pressure as well as pain stimuli. CONCLUSION: Together, ASICs are dual-function proteins for both chemosensation and mechanosensation involved in monitoring physiological homoeostasis and pathological signals.

Pd-Catalyzed Atroposelective C-H Olefination: Diverse Synthesis of Axially Chiral Biaryl-2-carboxylic Acids.

Axially chiral carboxylic acids are important motifs in chiral catalysts and ligands. We herein reported the synthesis of axially chiral carboxylic acids via Pd(II)-catalyzed atroposelective C-H olefination using carboxylic acid as the native directing group. A broad range of axial chiral biaryl-2-carboxylic acids were synthesized in good yields with high enantioselectivities (up to 84% yield with 99% ee). Gram-scale reaction and further transformation reactions also provide a platform for synthetic applications of this method.