A Versatile, Traceless C–H Activation-Based Approach for the Synthesis of Heterocycles

A versatile, traceless C–H activation-based approach for the synthesis of diversified heterocycles is reported. Rh­(III)-catalyzed, N-amino-directed C–H alkenylation generates either olefination products or indoles (in situ annulation) in an atom- and step-economic manner at room temperature. The remarkable reactivity endowed by this directing group enables scale-up of the reaction to a 10 g scale at a very low catalyst loading (0.01 mol %/0.1 mol %). Ex situ annulation of olefination product provides entry into an array of heterocycles

Rhodium(III)-Catalyzed Indole Synthesis Using N–N Bond as an Internal Oxidant

We report herein a Rh­(III)-catalyzed cyclization of <i>N</i>-nitrosoanilines with alkynes for streamlined synthesis of indoles. The synthetic protocol features a distinct internal oxidant, N–N bond, as a reactive handle for catalyst turnover, as well as a hitherto tantalizingly elusive intermolecular redox-neutral manifold, predicated upon C–H activation, for the formation of a five-membered azaheterocycle. The compatibility of seemingly dichotomous acidic and basic conditions ensures reaction versatility for multifarious synthetic contexts. The tolerance of an array of auxiliary functional groups potentially permits predefined, programmable substitution patterns to be incorporated into the indole scaffold. Comprehensive mechanistic studies, under acidic condition, support [RhCp*]²⁺ as generally the catalyst resting state (switchable to [RhCp*­(OOC^<i>t</i>Bu)]⁺ under certain circumstance) and C–H activation as the turnover-limiting step. Given the variety of covalent linkages available for the nitroso group, this labile functionality is likely to be harnessed as a generic handle for strikingly diverse coupling reactions

Rhodium(III)-Catalyzed Indole Synthesis Using N–N Bond as an Internal Oxidant

We report herein a Rh­(III)-catalyzed cyclization of <i>N</i>-nitrosoanilines with alkynes for streamlined synthesis of indoles. The synthetic protocol features a distinct internal oxidant, N–N bond, as a reactive handle for catalyst turnover, as well as a hitherto tantalizingly elusive intermolecular redox-neutral manifold, predicated upon C–H activation, for the formation of a five-membered azaheterocycle. The compatibility of seemingly dichotomous acidic and basic conditions ensures reaction versatility for multifarious synthetic contexts. The tolerance of an array of auxiliary functional groups potentially permits predefined, programmable substitution patterns to be incorporated into the indole scaffold. Comprehensive mechanistic studies, under acidic condition, support [RhCp*]²⁺ as generally the catalyst resting state (switchable to [RhCp*­(OOC^<i>t</i>Bu)]⁺ under certain circumstance) and C–H activation as the turnover-limiting step. Given the variety of covalent linkages available for the nitroso group, this labile functionality is likely to be harnessed as a generic handle for strikingly diverse coupling reactions

A Versatile, Traceless C–H Activation-Based Approach for the Synthesis of Heterocycles

A versatile, traceless C–H activation-based approach for the synthesis of diversified heterocycles is reported. Rh­(III)-catalyzed, <i>N</i>-amino-directed C–H alkenylation generates either olefination products or indoles (in situ annulation) in an atom- and step-economic manner at room temperature. The remarkable reactivity endowed by this directing group enables scale-up of the reaction to a 10 g scale at a very low catalyst loading (0.01 mol %/0.1 mol %). Ex situ annulation of olefination product provides entry into an array of heterocycles

Co(III)-Catalyzed, Internal and Terminal Alkyne-Compatible Synthesis of Indoles

A Co­(III)-catalyzed, internal and terminal alkyne-compatible indole synthesis protocol is reported herein. The <i>N</i>-amino (hydrazine) group imparts distinct, diverse reactivity patterns for directed C–H functionalization/cyclization reactions. Notable synthetic features include regioselectivity for a <i>meta</i>-substituted arylhydrazine, regioselectivity for a chain-branched terminal alkyne, formal incorporation of an acetylenic unit through C2-desilylation on a C2-silylated indole derivative, formal inversion of regioselectivity through consecutive C3-derivatization and C2-desilylation processes, and formal bond migration for a linear-chain terminal alkyne

Regioselective Formal [4 + 2] Cycloadditions of Enaminones with Diazocarbonyls through Rh^III-Catalyzed C–H Bond Functionalization

A regioselective formal [4 + 2] cycloaddition for the assembly of highly functionalized benzene rings was successfully developed. In this reaction, olefinic C–H bond functionalization/cyclization cascade reaction followed by rearomatization led to the desired molecules in one step under mild reaction conditions. This protocol also displays a broad substrate scope and good tolerance to a wide range of functional groups. Additionally, the potential utility for the synthesis of highly conjugated polybenzenes and diversification of natural products was also demonstrated

Bidentate Directing-Enabled, Traceless Heterocycle Synthesis: Cobalt-Catalyzed Access to Isoquinolines

Traceless heterocycle synthesis based on transition-metal-catalyzed C–H functionalization is synthetically appealing but has been realized only in monodentate directing systems. Bidentate directing systems allow for the achievement of high catalytic reactivity without the need for a high-cost privileged ligand. The first bidentate directing-enabled, traceless heterocycle synthesis is demonstrated in the cobalt-catalyzed synthesis of isoquinolines via 2-hydrazinylpyridine-directed C–H coupling/cyclization with alkynes. Convenient directing group installation through a ubiquitously present ketone group allows synthetic elaboration for complex molecules

Co(III)-Catalyzed, Internal and Terminal Alkyne-Compatible Synthesis of Indoles

A Co­(III)-catalyzed, internal and terminal alkyne-compatible indole synthesis protocol is reported herein. The <i>N</i>-amino (hydrazine) group imparts distinct, diverse reactivity patterns for directed C–H functionalization/cyclization reactions. Notable synthetic features include regioselectivity for a <i>meta</i>-substituted arylhydrazine, regioselectivity for a chain-branched terminal alkyne, formal incorporation of an acetylenic unit through C2-desilylation on a C2-silylated indole derivative, formal inversion of regioselectivity through consecutive C3-derivatization and C2-desilylation processes, and formal bond migration for a linear-chain terminal alkyne

Summary of clinic pathological parameters of patients with osteosarcoma.

Summary of clinic pathological parameters of patients with osteosarcoma.</p

The Downregulation of MiR-182 Is Associated with the Growth and Invasion of Osteosarcoma Cells through the Regulation of TIAM1 Expression

<div><p>Background</p><p>Osteosarcoma is the most common primary bone malignancy in children and young adults. Increasing results suggest that discovery of microRNAs (miRNAs) might provide a novel therapeutical target for osteosarcoma.</p><p>Methods</p><p>MiR-182 expression level in osteosarcoma cell lines and tissues were assayed by qRT-PCR. MiRNA mimics or inhibitor were transfected for up-regulation or down-regulation of miR-182 expression. Cell function was assayed by CCK8, migration assay and invasion assay. The target genes of miR-182 were predicated by bioinformatics algorithm (TargetScan Human).</p><p>Results</p><p>MiR-182 was down-regulated in osteosarcoma tissues and cell lines. Overexpression of miR-182 inhibited tumor growth, migration and invasion. Subsequent investigation revealed that TIAM1 was a direct and functional target of miR-182 in osteosarcoma cells. Overexpression of miR-182 impaired TIAM1-induced inhibition of proliferation and invasion in osteosarcoma cells.</p><p>Conclusions</p><p>Down-expression of miR-182 in osteosarcoma promoted tumor growth, migration and invasion by targeting TIAM1. MiR-182 might act as a tumor suppressor gene whose down-regulation contributes to the progression and metastasis of osteosarcoma, providing a potential therapy target for osteosarcoma patients.</p></div