Kyungsoo Oh

G-protein-coupled receptor 41 (GPR41/FFAR3) functions as a crucial metabolic sensor of gut microbiota-derived short-chain fatty acids (SCFAs). However, the precise mechanisms by which GPR41 suppresses metabolic endotoxemia caused by translocation of gut-derived lipopolysaccharide (LPS) into the circulation remain unclear. In this study, we investigated the protective effects of AR420626 (AR), a selective GPR41 agonist, against endotoxemia using RAW 264.7 macrophages to mimic an endotoxin stress environment. Our results showed that AR-induced activation of GPR41 significantly suppressed the production of nitric oxide (NO) and interleukin-6 (IL-6), key pro-inflammatory mediators implicated in the pathogenesis of endotoxemia, through inhibition of the nuclear factor kappa B (NF-κB) signaling pathway. In addition, AR-mediated GPR41 activation significantly reduced the expression of monocyte chemoattractant protein-1 (MCP-1) and inducible nitric oxide synthase (iNOS). These protective effects were mechanistically linked to enhanced autophagic activity, as evidenced by increased conversion of LC3-I to LC3-II. Importantly, pharmacological inhibition of autophagy abolished the ability of AR to suppress NF-κB activation, suggesting that the GPR41-autophagy axis is essential for preserving macrophage homeostasis against LPS-induced endotoxemia damage. Furthermore, GPR41 knockdown markedly abrogated the AR-mediated regulation of iNOS, phosphorylated NF-κB, and p62 under LPS stimulation, confirming that these protective effects are specifically mediated through GPR41. These results suggest that pharmacological activation of GPR41 to enhance autophagy may represent a novel therapeutic strategy for the treatment of endotoxemia.

The hexafluoroisopropanol (HFIP)-assisted thermal denitrogenative fragmentation of areneazo-2-(2-nitro)propanes enabled heteroarylation of functionalized alkenes through cooperative radical and redox processes. Bench-stable areneazo-2-(2-nitro)propanes served as versatile aryl radical precursors for carboheterocyclization with alkenyl esters, affording diverse arylated lactones and heterocycles with broad functional group tolerance. Mechanistically, the radical fragmentation–nitro–nitrite isomerization of areneazo-2-(2-nitro)propanes generated nitric oxide that underwent a redox process with tertiary radical intermediates to promote heterocyclization. The oxidant-free conditions generated dinitrogen and acetone as benign byproducts.

This work reports the stereoselective total synthesis and structural revision of menominins A (1) and B (2) featuring a 3,8-dihydroxy-2-methyltetradecanoic acid residue with a (2R,3R,8S) configuration as a key stereochemical element. This strategy features Evans aldol reactions, Mitsunobu inversion, and ring-closing metathesis as the key steps. Extensive analysis of the spectral data for the synthetic material, combined with reported data, led to structural revisions of menominins A (1) and B (2).

Visible light‐driven transformations offer an attractive strategy for sustainable synthesis by simplifying reaction systems while maintaining high efficiency. Herein, we report an exogenous photocatalyst‐free visible light‐induced three‐component 1,2‐acylarylation of quinoxalin‐2(1 H )‐ones with styrenes and acyl oxime esters under mild conditions. Exploiting the intrinsic photoactivity of quinoxalin‐2(1 H )‐ones, direct excitation under purple LED irradiation enables single electron transfer (SET) to acyl oxime esters, generating acyl radicals without the need for external photocatalysts. The resulting radicals undergo a sequential addition to alkenes and quinoxalin‐2(1 H )‐ones, affording structurally diverse C3‐functionalized products in moderate to good yields. The current three‐component coupling protocol exhibits broad substrate scope, tolerating a range of styrenes, quinoxalin‐2(1 H )‐ones, and benzoyl oxime esters. Mechanistic studies, including radical trapping experiments, fluorescence quenching, and UV–Vis analysis, support a SET‐driven radical relay pathway involving a photoexcited quinoxalin‐2(1 H )‐one. This operationally simple and modular approach highlights the dual role of quinoxalin‐2(1 H )‐ones as both substrate and photoactive species, expanding the scope of exogenous photocatalyst‐free multicomponent radical transformations.

Aerobic sulfonyloximation of alkenes has been developed using the commodity chemical 2-nitropropane as dual sources of α-nitroalkyl radicals and nitric oxide (NO) under cooperative KSeCN/TBAI phase transfer catalysis. This method enables concurrent C-SO₂R and C-NO bond formation through a radical redox relay involving aerobic nitro-nitrite isomerization and NO fragmentation. Structurally diverse β-sulfonyl oximes with broad substrate scope are obtained under mild conditions, highlighting the potential of controlled NO incorporation in radical transformations.

Modulating the redox potential of organic substrates is a powerful strategy for steering electrochemical reaction pathways, particularly for systems capable of undergoing both oxidation and reduction. Herein, we report the first electrochemical cyclization of areneazo‐2‐(2‐nitro)propanes to benzo[ c ]cinnolines enabled by solvent‐mediated redox pathway control. Careful selection of the reaction medium, especially mixed solvent systems containing hexafluoroisopropanol (HFIP) and alcohol additives, not only widens the redox potential gap between oxidation and reduction events but also stabilizes key intermediates through hydrogen‐bonding interactions, thereby favoring oxidative intramolecular cyclization over competing denitrogenative reduction pathways. Cyclic voltammetry reveals a clear correlation between solvent‐dependent redox windows and reaction outcomes, underscoring the decisive role of solvent effects in governing electrochemical selectivity. Under optimized constant current conditions using graphite electrodes, a broad range of areneazo‐2‐(2‐nitro)propanes undergo efficient cyclization to afford benzo[ c ]cinnolines in good yields. Mechanistic studies support a pathway involving MeOH‐stabilized diazonium intermediates and controlled redox fragmentation, demonstrating how strategic solvent engineering can unlock new electrochemical transformations of redox‐active organic substrates.

An aerobic carboheterocyclization of functionalized alkenes has been developed using secondary nitroalkanes as dual sources of α-nitroalkyl radicals and nitric oxide (NO) under cooperative phase transfer catalysis of KSeCN and TBAI. This method enables efficient synthesis of nitrogen- and oxygen-containing heterocycles via radical redox interplay between nitric oxide and tertiary carbon radicals. The current study highlights the mechanistic role of aerobic nitro–nitrite isomerization and expands the synthetic utility of radical-mediated tandem cyclizations under aerobic conditions.

The development of general anti-Markovnikov hydroalkoxylation methods remains challenging due to competing alkene oxidation and photocatalyst-alcohol compatibility issues. Herein, diaryl diselenides serve as efficient electron-shuttle catalysts for visible-light-driven anti-Markovnikov hydroalkoxylation in combination with TPT⁺BF₄^-. A broad range of aryl- and alkyl-substituted alkenes and diverse alcohols are accommodated, affording products up to 97% yield. Mechanistic studies reveal a diselenide-mediated, multistep electron-shuttle pathway that enables mild and selective transformations.

Copper‐ and silver‐catalyzed reactions of active methylene isocyanides provide powerful and versatile strategies for the construction of heterocyclic architectures relevant to pharmaceutical and materials science. Owing to their unique ambiphilic reactivity, active methylene isocyanides serve as key building blocks for the synthesis of fused, bicyclic, polycyclic, and spirocyclic heterocycles under mild catalytic conditions. This review summarizes recent advances in the copper‐ and silver‐catalyzed transformation of functionalized isocyanides toward multi‐substituted five‐ and six‐membered heterocyclic frameworks. Particular emphasis is placed on [3+ n ] cycloaddition reactions, as well as tandem processes involving cycloaddition, annulation, alkylation, and insertion pathways. In addition, emerging strategies that exploit nonfunctionalized isocyanides, strained alkene surrogates, and multi‐isocyanide reaction manifolds are discussed, highlighting new opportunities for complexity generation and asymmetric heterocycle synthesis.

The aerobic oxidation of alcohols is valuable but often limited by toxic reagents, waste, and harsh conditions. Using a Ru³⁺-hydroxyapatite (RuHAP)-packed-bed reactor under low-pressure O₂, we achieved efficient, reproducible oxidations with TONs of >18,000 after two catalyst regenerations. A two-step continuous flow process integrating oxidation and Knoevenagel condensation delivered products in excellent yields, demonstrating a scalable, safe, and sustainable method with high selectivity and mild conditions for fine chemical and pharmaceutical synthesis.