Atroposelective Synthesis of Pyridoindolones Bearing Two Remote Distinct C-N Axes through Cobalt-Catalyzed Enantioselective C-H Activation.

C-N axially chiral compounds represent an important class of atropisomers that are prevalent in bioactive and material molecules. Despite recent advances in synthetic methodologies, the asymmetric construction of atropisomers featuring multiple C-N axes has been rarely explored, significantly limiting their further applications. Herein, we report a novel atroposelective synthesis of diaxially chiral pyridoindolones featuring both six-five and six-six C-N axes through cobalt-catalyzed asymmetric C-H annulation.

Exploring the underlying molecular connections: a bioinformatics approach to link melanoma and Parkinson's disease.

Introduction: Melanoma, a highly aggressive form of skin cancer, and Parkinson's disease (PD), a progressive neurodegenerative disorder, have been epidemiologically linked, showing a positive association that suggests a shared etiology. This association implies that individuals with one condition may have an increased risk of developing the other. However, the specific molecular mechanisms underlying this relationship remain unclear.

Cobalt(III)-Catalyzed Enantioselective C-H Functionalization: Ligand Innovation and Reaction Development.

ConspectusIn contrast to precious transition metals, such as palladium and rhodium, the development of novel chiral ligands for enantioselective C-H functionalizations catalyzed by earth-abundant, cost-effective, and environmentally friendly 3d metals poses substantial challenges, primarily due to the variable oxidation states, intricate coordination patterns, and limited mechanistic insights. In this Account, we summarize our research endeavors in the development of three novel types of Co(III) catalysis: pseudotetrahedral achiral Cp*Co(III)/chiral carbonyl acid (CCA) catalysis, -generated chiral octahedral cobalt(III) via cobalt/salicyloxazoline (Salox) catalysis, and Co(II)/chiral phosphoric acid (CPA) cooperative catalysis, achieved through strategic chiral ligand design. Our initial objective was to achieve enantioselective C-H functionalization catalyzed by achiral Cp*Co(III) catalysts with external chiral ligands, aiming to circumvent the laborious preparation of chiral CpCo(III) complexes.

Efficacy and safety of reduced-port laparoscopic surgery versus conventional laparoscopic surgery for colorectal cancer.

Background: Laparoscopic radical resection has become the most important treatment for resectable colorectal cancer (CRC). However, there is still a lack of researches on the efficacy and safety of reduced-port laparoscopic surgery (RPLS) versus conventional laparoscopic surgery (CLS) in the treatment of CRC.

Patients And Methods: From January 2019 to July 2022, 698 patients with CRC received surgical treatment in the Sixth Affiliated Hospital of Sun Yat-sen University were enrolled in this retrospective cohort study.

Copper-Mediated Enantioselective C-H Thiolation of Ferrocenes Enabled by the BINOL Ligand.

Transition-metal-catalyzed enantioselective C-H activation has transformed the landscape of asymmetric synthesis, enabling the efficient conversion of C-H bonds into C-C and carbon-heteroatom (C-X) bonds. However, the formation of C-S bonds through enantioselective C-H thiolation remains underdeveloped due to challenges such as catalyst deactivation and competitive coordination of sulfur-containing compounds with chiral ligands. Herein, we report an unprecedented approach to constructing sulfur-substituted planar chiral ferrocenes (PCFs) through copper-mediated enantioselective C-H thiolation enabled by only a 2.

Nickel(II)/Salox-Catalyzed Enantioselective C-H Functionalization.

Recently, nickel catalysts have garnered considerable attention for their efficacy and versatility in asymmetric catalysis, attributed to their distinctive properties. However, the use of cost-effective and sustainable divalent nickel catalysts in C-H activation/asymmetric alkene insertion poses significant challenges due to the intricate control of stereochemistry in the transformation of the tetracoordinate C-Ni(II) intermediate. Herein, we report a Ni(II)-catalyzed enantioselective C-H/N-H annulation with oxabicyclic alkenes.

Asymmetric Synthesis of Chiral Calix[4]arenes with Both Inherent and Axial Chirality via Cobalt-Catalyzed Enantioselective Intermolecular C-H Annulation.

Inherently chiral calixarenes have garnered significant attention due to their distinctive properties, yet the development of efficient catalytic asymmetric synthesis methods remains a critical challenge. Herein, we report the asymmetric synthesis of calix[4]arenes featuring inherent or both inherent and axial chirality via a cobalt-catalyzed C-H activation/annulation strategy in high yield with excellent enantio- and diastereoselectivity (up to >99 % ee and >20 : 1 dr). Electrooxidation was also suitable for this transformation to obviate the sacrificial metal oxidants, underscoring the environmentally friendly potential of this approach.

Nickel(II)/BINOL-catalyzed enantioselective C-H activation via desymmetrization and kinetic resolution.

The field of nickel catalysis has witnessed remarkable growth in recent years. However, the use of nickel catalysts in enantioselective C-H activation remains a daunting challenge because of their variable oxidation states, intricate coordination chemistry, and unpredictable reactivity patterns. Herein, we report an enantioselective C-H activation reaction catalyzed by commercially available and air-stable nickel(II) catalyst.

EZH2-H3K27me3-Mediated Epigenetic Silencing of DKK1 Induces Nucleus Pulposus Cell Pyroptosis in Intervertebral Disc Degeneration by Activating NLRP3 and NAIP/NLRC4.

Nucleus pulposus (NP) cell pyroptosis is crucial for intervertebral disc degeneration (IDD). However, the precise mechanisms underlying pyroptosis in IDD remain elusive. Therefore, this study aimed to investigate how dickkopf-1 (DKK1) influences NP cell pyroptosis and delineate the regulatory mechanisms of IDD.

MFAP2 induces epithelial-mesenchymal transformation of osteosarcoma cells by activating the Notch1 pathway.

Background: Osteosarcoma (OS) is a malignancy originating from mesenchymal tissue. Microfibril-associated protein 2 () plays a crucial role in cancer, notably promoting epithelial-mesenchymal transition (EMT). However, its involvement in OS remains unexplored.

Asymmetric Dearomatization of Indoles through Cobalt-Catalyzed Enantioselective C-H Functionalization Enabled by Photocatalysis.

Photocatalysis holds a pivotal position in modern organic synthesis, capable of inducing novel reactivities under mild and environmentally friendly reaction conditions. However, the merger of photocatalysis and transition-metal-catalyzed asymmetric C-H activation as an efficient and sustainable method for the construction of chiral molecules remains elusive and challenging. Herein, we develop a cobalt-catalyzed enantioselective C-H activation reaction enabled by visible-light photoredox catalysis, providing a synergistic catalytic strategy for the asymmetric dearomatization of indoles with high levels of enantioselectivity (96 % to >99 % ee).

PD-1 blockade enhances the effect of targeted chemotherapy on locally advanced pMMR/MSS colorectal cancer.

Background: Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies).

Cobalt-Catalyzed Domino Transformations via Enantioselective C-H Activation/Nucleophilic [3 + 2] Annulation toward Chiral Bridged Bicycles.

Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C-H activation constitutes substantial challenges due to the multiple reactivities of strained bicyclic structures. Herein, we develop the domino transformations through an unprecedented cobalt-catalyzed enantioselective C-H activation/nucleophilic [3 + 2] annulation with symmetrical bicyclic alkenes. The methods offer straightforward access to a wide range of chiral molecules bearing [2.

Cobalt-Catalyzed Enantioselective C-H Carbonylation towards Chiral Isoindolinones.

Transition metal-catalyzed enantioselective C-H carbonylation with carbon monoxide, an essential and easily available C1 feedstock, remains challenging. Here, we disclosed an unprecedented enantioselective C-H carbonylation catalyzed by inexpensive and readily available cobalt(II) salt. The reactions proceed efficiently through desymmetrization, kinetic resolution, and parallel kinetic resolution, affording a broad range of chiral isoindolinones in good yields with excellent enantioselectivities (up to 92 % yield and 99 % ee).

Soy isoflavones induces mitophagy to inhibit the progression of osteosarcoma by blocking the AKT/mTOR signaling pathway.

Background: Soy isoflavones (SI) is a natural bioactive substance exhibiting beneficial effects on human health. This study aims to elucidate the therapeutic potential of SI in the treatment of osteosarcoma (OS) and to investigate the underlying mechanisms, particularly focusing on mitophagy.

Methods: The effects of SI on the proliferation, apoptosis, migration, and invasion of U2OS cells were analyzed.

Cobalt-Catalyzed Enantioselective C-H Annulation of Benzylamines with Alkynes: Application to the Modular and Asymmetric Syntheses of Bioactive Molecules.

The transition metal-catalyzed enantioselective C-H functionalization strategy has revolutionized the logic of natural product synthesis. However, previous applications have heavily relied on the use of noble metal catalysts such as rhodium and palladium. Herein, we report the efficient synthesis of C-chiral 1,2-dihydroisoquinolines (DHIQs) via enantioselective C-H/N-H annulation of picolinamides with alkynes catalyzed by a more sustainable and cheaper 3d metal catalyst, cobalt(II) acetate tetrahydrate.

Pd(II)-Catalyzed atroposelective C-H olefination: synthesis of enantioenriched -aryl peptoid atropisomers.

Herein, we reported the synthesis of enantioenriched -aryl peptoid atropisomers Pd(II)-catalyzed atroposelective C-H olefination using the easily accessible L-pyroglutamic acid (L-Glu-OH) as the chiral ligand. A series of optically active -aryl peptoid atropisomers were obtained in synthetically useful yields with high enantioselectivities.

Synthesis of Axially Chiral Biaryls through Cobalt(II)-Catalyzed Atroposelective C-H Arylation.

Highly efficient synthesis of axially chiral biaryl amines through cobalt-catalyzed atroposelective C-H arylation using easily accessible cobalt(II) salt and salicyloxazoline ligand has been reported. This methodology provides a straightforward and sustainable access to a broad range of enantioenriched biaryl-2-amines in good yields (up to 99 %) with excellent enantioselectivities (up to 99 % ee). The synthetic utility of the unprecedented method is highlighted by its scalability and diverse transformations.

Synthesis of Chiral Diarylmethylamines by Cobalt-Catalyzed Enantioselective C-H Alkoxylation.

Chiral diarylmethylamines (DAMA) are important structural motifs widely present in pharmaceuticals, natural products, and chiral ligands. Herein, we reported a highly enantioselective synthesis of chiral DAMAs via cobalt-catalyzed enantioselective C-H alkoxylation strategy. The reaction features easy operation, the use of earth-abundant and cost-efficient cobalt(II) catalyst, and readily available ligand.

Base-Promoted Electrochemical Co -catalyzed Enantioselective C-H Oxygenation.

Metalla-electrocatalyzed C-H oxygenation represents one of the most straightforward and sustainable approaches to access valuable oxygenated molecules. Despite the significant advances, the development of enantioselective electrochemical C-H oxygenation reaction is very challenging and remains elusive. Herein, we described the first electrochemical Co -catalyzed enantioselective C-H alkoxylation.

Enantio- and Regioselective Electrooxidative Cobalt-Catalyzed C-H/N-H Annulation with Alkenes.

In recent years, the merging of electrosynthesis with 3d metal catalyzed C-H activation has emerged as a sustainable and powerful technique in organic synthesis. Despite the impressive advantages, the development of an enantioselective version remains elusive and poses a daunting challenge. Herein, we report the first electrooxidative cobalt-catalyzed enantio- and regioselective C-H/N-H annulation with olefins using an undivided cell at room temperature (up to 99 % ee).

Single-Agent Neoadjuvant Immunotherapy With a PD-1 Antibody in Locally Advanced Mismatch Repair-Deficient or Microsatellite Instability-High Colorectal Cancer.

Background: PD-1 blockade has been recommended as first-line therapy for nonresectable or metastatic mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, the safety and efficacy of neoadjuvant PD-1 blockade immunotherapy for locally advanced dMMR/MSI-H CRC remain unclear.

Patients And Methods: From June 2020 to June 2022, 11 locally advanced dMMR/MSI-H CRC patients treated at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were enrolled.