Photomediated One-Pot Three-Component Approach Enables the Formal Direct -Acylation/Sulfonylation and α-C-H Functionalization of 1,2,3,4-Tetrahydroisoquinoline.

-Acyl/sulfonyl-α-functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) are significant structural motifs in organic synthesis and drug discovery. However, the one-pot approach enabling direct difunctionalization of THIQs remains challenging. Herein we report a photomediated one-pot three-component strategy to access -acyl/sulfonyl-α-functionalized THIQs.

Regioselective Homolytic C-H Borylation of Unprotected Adenosine and Adenine Derivatives via Minisci Reaction.

A Minisci-type borylation of unprotected adenosine, adenine nucleotide, and adenosine analogues was successfully achieved through photocatalysis or thermal activation. Despite the challenges posed by the presence of two potential reactive sites (C and C) in the purine motif, the unique nucleophilic amine-ligated boryl radicals effortlessly achieved excellent C site selectivity and simultaneously avoided the formation of multifunctionalized products. This protocol proved effective for the late-stage borylation of some important biomolecules as well as a few antiviral and antitumor drug molecules, such as AMP, cAMP, Vidarabine, Cordycepin, Tenofovir, Adefovir, GS-441524, etc.

Integrating carbon dots and gold/silver core-shell nanoparticles to achieve sensitive detection of dopamine with fluorometric/colorimetric dual signal.

Dopamine (DA) is a potent neuromodulator in the brain that affects a wide range of motivated behaviors. Abnormal concentration of DA is related to a variety of diseases. Hence, it is imperative to establish a rapid and precise method for quantifying DA.

Synthesis of β-Carbonyl α-Iminoamides by Double Insertion of Isocyanides into Aldehydes.

An unprecedented trimethylsilyl trifluoromethanesulfonate (TMSOTf)-promoted selective double insertion of isocyanides into aldehydes was developed, providing an efficient protocol for synthetically challenging β-carbonyl α-iminoamides. The given approach is applicable for a diverse selection of readily accessible aldehydes, along with isocyanides serving as essential precursors for "amide" and "imine" scaffolds. The versatile transformations of the given products were demonstrated, and the pivotal intermediates for the plausible mechanism were identified.

Surface saturation of drug-loaded hollow manganese dioxide nanoparticles with human serum albumin for treating rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease accompanied by energy depletion and accumulation of reactive oxygen species (ROS). Inorganic nanoparticles (NPs) offer great promise for the treatment of RA because they mostly have functions beyond being drug carriers. However, conventional nanomaterials become coated with a protein corona (PC) or lose their cargo prematurely , reducing their therapeutic efficacy.

7-Amino-3-phenyl-2-methyl-pyrazolopyrimidine derivatives inhibit human rhinovirus replication.

Small molecules that exhibit broad-spectrum enteroviral inhibitory activity by targeting viral replication proteins are highly desired in antiviral drug discovery studies. To discover new human rhinovirus (hRV) inhibitors, we performed a high-throughput screening of 100,000 compounds from the Korea Chemical Bank library. This search led to identification of two phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) inhibitors having the pyrazolo-pyrimidine core structure, which display moderate anti-rhinoviral activity along with mild cytotoxicity.

Catalytic asymmetric intramolecular propargylation of cyclopropanols to access the cuparane core.

The catalytic asymmetric propargylation of enol(ate) intermediates is a well-established method for the synthesis of α-propargyl-substituted carbonyl compounds. However, the propargylation of homo-enol(ate) or its equivalents for the synthesis of β-propargyl-substituted carbonyl compounds remains underdeveloped. A catalytic enantioselective decarboxylative intramolecular propargylation of cyclopropanols has been developed using a PyBox-complexed copper catalyst.

Effects of different post-harvest processing methods on changes in the active ingredients of licorice based on LC-MS and plant metabolomics.

Introduction: Licorice, the dried roots and rhizomes of the Glycyrrhiza uralensis Fisch., holds a prominent status in various formulations within the realm of Chinese medicinal practices. The traditional processing methods of licorice hinder quality assurance, thus prompting Chinese medicine researchers to focus on the fresh processing methods to enhancing processing efficiency and quality.

De Novo Synthesis of α-Ketoamides via Pd/TBD Synergistic Catalysis.

Precisely controlling the product selectivity of a reaction is an important objective in organic synthesis. α-Ketoamides are vital intermediates in chemical transformations and privileged motifs in numerous drugs, natural products, and biologically active molecules. The selective synthesis of α-ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long-standing catalysis challenge.

Desulfurization of Thiols for Nucleophilic Substitution.

Although the desulfurization of thiols is a topic of great importance and has received significant attention, most efforts have focused on the hydrodesulfurization of thiols. In this work, we describe the desulfurization of thiols for nucleophilic substitution. This process occurs rapidly, promoted by the PhP/ICHCHI system, and can be extended to a wide range of nucleophiles.

Carbon Dot Nanozyme Ameliorating Ischemia-Reperfusion-Induced Muscle Injury by Antioxidation and Downregulating iNOS/COX-2 Pathway.

Skeletal muscle ischemia-reperfusion (IR) injury is a prevalent type of muscle injury caused by events, such as trauma, arterial embolism, and primary thrombosis. The development of an IR injury is associated with oxidative stress and an excessive inflammatory response. Nanozymes, which have exceptional free radical scavenging activities, have gained significant attention for treating oxidative stress.

DNA encoded peptide library for SARS-CoV-2 3CL protease covalent inhibitor discovery and profiling.

Covalent protease inhibitors serve as valuable tools for modulating protease activity and are essential for investigating the functions of protease targets. These inhibitors typically consist of a recognition motif and a covalently reactive electrophile. Substrate peptides, featuring residues capable of fitting into the substrate pockets of proteases, undergo chemical modification at the carbonyl carbon of the P1 residue with an electrophile and have been widely applied in the development of covalent inhibitors.

Discovery and optimization of 3-(indolin-5-yloxy)pyridin-2-amine derivatives as potent necroptosis inhibitors.

Necroptosis is a form of regulated necrotic cell death and has been confirmed to play pivotal roles in the pathogenesis of multiple autoimmune diseases such as rheumatoid arthritis (RA) and psoriasis. The development of necroptosis inhibitors may offer a promising therapeutic strategy for the treatment of these autoimmune diseases. Herein, starting from the in-house hit compound 1, we systematically performed structural optimization to discover potent necroptosis inhibitors with good pharmacokinetic profiles.

NUAK2 Inhibitors, KHKI-01128 and KHKI-01215, Exhibit Potent Anticancer Activity Against SW480 Colorectal Cancer Cells.

Background/aim: NUAK family kinase 2 (NUAK2) is a promising target for cancer therapeutics due to its reported role in protein phosphorylation, a critical process in cancer cell survival, proliferation, invasion, and senescence. This study aimed to identify novel inhibitors that disrupt NUAK2 activity. We have already identified two KRICT Hippo kinase inhibitor (KHKI) compounds, such as KHKI-01128 and KHKI-01215.

Reaction Templates: Bridging Synthesis Knowledge and Artificial Intelligence.

ConspectusThe field of chemical research boasts a long history of developing software to automate synthesis planning and reaction prediction. Early software relied heavily on expert systems, requiring significant effort to encode vast amounts of synthesis knowledge into a computer-readable format. However, recent advancements in deep learning have shifted the focus toward AI models, offering improved prediction capabilities.

Significant Interaction between Melatonin and Titanium Bone Implants: Available Evidence and Future Research Directions.

The trend in the incidence rate of bone fractures has been upward and as a result, the burden associated with orthopedic fractures has increased significantly. Titanium (Ti) implants are considered a preferred method of managing long bone fractures. However, no benefit comes without some downside, and using Ti implants is associated with several complications.

Five Pairs of Enantiomer as Rearrangement Products from Secoiridoids in Pall.

Five racemates () were isolated from , in which were successfully separated into four pairs of enantiomers ( and , and , and , and and ), whereas the resolution of failed due to the hemiacetal functionality at the stereogenic center. Using electronic circular dichrosim calculation, the relationship of the molecular rotation direction and the carbon / chirality was revealed, and each pair of enantiomer was identified as (-)-()-gentianmacrol B () and (+)-()-gentianmacrol B (), (-)-()-8-methoxy-gentianol () and (+)-()-8-methoxy-gentianol (), (+)-()-8-methyl-gentianadine () and (-)-()-8-methyl-gentianadine (), and (-)-()-gentianol () and (+)-()-gentianol (). Besides, these compounds could be divided into two series, containing the benzene ring moiety and containing the pyridine ring moiety.

Highly accurate carbohydrate-binding site prediction with DeepGlycanSite.

As the most abundant organic substances in nature, carbohydrates are essential for life. Understanding how carbohydrates regulate proteins in the physiological and pathological processes presents opportunities to address crucial biological problems and develop new therapeutics. However, the diversity and complexity of carbohydrates pose a challenge in experimentally identifying the sites where carbohydrates bind to and act on proteins.