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A chiral N,N′-dioxide/Co(BF4)2·6H2O complex catalytic system has been developed to efficiently catalyze the asymmetric 1,3-dipolar cycloaddition of nitrones with methyleneindolinones. The corresponding chiral multisubstituted spiroisoxazolidines with three contiguous quaternary–tertiary stereocenters were obtained in moderate to high yields with excellent dr and ee values (up to 97% yield, ＞19 : 1 dr and 98% ee). [ABSTRACT FROM AUTHOR]

New Ir complexes bearing N-(methylsulfonyl)-2-pyridinecarboxamide (C1) and N-(phenylsulfonyl)-2-pyridinecarboxamide (C2) were employed as catalysts for aqueous formic acid dehydrogenation (FADH). The ligands were designed to maintain the picolinamide skeleton and introduce strong sigma sulfonamide moieties. C1 and C2 exhibited good stability towards air and concentrated formic acid (FA). During 20 continuous cycles, C1 and C2 could achieve the complete conversion of FA with TONs of 172 916 and 172 187, respectively. C1 achieved a high TOF of 19 500 h−1 at 90 °C and an air-stable Ir–H species was observed by 1H NMR spectroscopy. [ABSTRACT FROM AUTHOR]

The highly catalytic asymmetric α-hydroxylation of 1-tetralone-derived β-keto esters and β-keto amides using tert-butyl hydroperoxide (TBHP) as the oxidant was realized by a chiral N, N′-dioxide-magnesium ditriflate [Mg(OTf)2] complex. A series of corresponding chiral α-hydroxy dicarbonyl compounds was obtained in excellent yields (up to 99%) with excellent enantioselectivities (up to 98% ee). The products were easily transformed into useful building blocks and the precursor of daunomycin was achieved in an asymmetric catalytic way for the first time. [ABSTRACT FROM AUTHOR]

An asymmetric 1,3-dipolar cycloaddition of methyleneoxindoles and cyclic azomethine imines affords spirocyclic pyrazolidines in excellent yields and enantioselectivities under mild reaction conditions. [ABSTRACT FROM AUTHOR]

Chiral N,N-dioxide magnesium complexes are described as efficient catalysts for the α-hydroxylation of cyclic 1-tetralone derived β-keto esters. [ABSTRACT FROM AUTHOR]

[Display omitted] • KYS202004A, a novel bispecific protein, antagonizes TNF-α and IL-17A simultaneously. • Superior to monotherapies in reducing disease markers in arthritis and psoriasis models. • Demonstrates robust inhibition of cytokine-induced CXCL1 expression in vitro. • Offers a dual-targeted therapeutic approach, enhancing efficacy over current treatments. The treatment of autoimmune and inflammatory diseases often requires targeting multiple pathogenic pathways. KYS202004A is a novel bispecific fusion protein designed to antagonize TNF-α and IL-17A, pivotal in the pathophysiology of autoimmune and inflammatory diseases. Our initial efforts focused on screening for optimal structure by analyzing expression levels, purity, and binding capabilities. The binding affinity of KYS202004A to TNF-α and IL-17A was evaluated using SPR. In vitro, we assessed the inhibitory capacity of KYS202004A on cytokine-induced CXCL1 expression in HT29 cells. In vivo, its efficacy was tested using a Collagen-Induced Arthritis (CIA) model in transgenic human-IL-17A mice and an imiquimod-induced psoriasis model in cynomolgus monkeys. KYS202004A demonstrated significant inhibition of IL-17A and TNF-α signaling pathways, outperforming the efficacy of monotherapeutic agents ixekizumab and etanercept in reducing CXCL1 expression in vitro and ameliorating disease markers in vivo. In the CIA model, KYS202004A significantly reduced clinical symptoms, joint destruction, and serum IL-6 concentrations. The psoriasis model revealed that KYS202004A, particularly at a 2 mg/kg dose, was as effective as the combination of ixekizumab and etanercept. This discovery represents a significant advancement in treating autoimmune and inflammatory diseases, offering a dual-targeted therapeutic approach with enhanced efficacy over current monotherapies. [ABSTRACT FROM AUTHOR]

The highly efficient catalytic asymmetric inverse-electron-demand hetero-Diels–Alder reaction of methyleneindolinones with hetero-substituted alkenes has been accomplished under mild reaction conditions. In the presence of chiral N,N′-dioxide/Ni(ii) complexes, a wide range of optically active dihydropyran-fused indoles were obtained in up to 99% yield, ＞95 : 5 dr and 99% ee. [ABSTRACT FROM AUTHOR]

The scalable title reaction of various methyleneindolinones with mono- and 1,1-disubstituted acyclic vinyl ethers, ethylvinyl sulfide (X) and dihydropyran (XII) delivers the corresponding products in high yield, with high to excellent diastereomeric excess and with excellent enantioselectivity. [ABSTRACT FROM AUTHOR]

This new process proceeds under mild conditions, exhibits a broad substrate scope and functional-group tolerance, and features good air and moisture tolerance. [ABSTRACT FROM AUTHOR]