Iron is an abundant metal in the earth's crust and possesses excellent biocompatibility, making the development of iron photocatalysis highly desirable for green and sustainable chemistry. In recent years, photoinduced iron catalysis driven by ligand-to-metal charge transfer (LMCT) has witnessed significant progress. This strategy involves the photoexcitation of iron-substrate (or reagent) complexes to induce intramolecular electron transfer, generating highly reactive radical species that trigger diverse organic transformations under mild conditions. The recent advances in ligand-facilitated LMCT-driven photoinduced iron catalysis are systematically summarized. The discussions are categorized based on the types of substrates (or reagents) involved in the LMCT process, covering systems such as alkyl carboxylic acids, oxamic acids, fluorinated alkyl carboxylic acids, aryl carboxylic acids, alcohols, water, azides, and chlorides. Special emphasis is placed on the critical role of ligands (e.g., picolinic acids, polypyridyl amines) in tuning the redox properties of the iron center, prolonging excited-state lifetimes, and enhancing visible light absorption. The reaction mechanisms and synthetic applications are also discussed. Finally, the challenges and future prospects of this emerging field are highlighted.

The precise control of reaction trajectories remains a formidable challenge in photochemical synthesis, particularly for conjugated dienes whose consecutive pi-systems give rise to multiple competing reaction pathways. Herein, we report a divergent synthetic platform enabled by visible-light-induced energy transfer (EnT) catalysis. By exploiting how cyclic conjugated dienes accommodate or restrict the requisite torsional distortion of the cyclic backbone to form a trans-cycloalkene intermediate, this strategy dictates their photochemical fate, elegantly channeling reactivity into three distinct manifolds through ring-dependent kinetic control. Through strategic manipulation of skeletal parameters-such as ring size, geometric rigidity, and steric hindrance-we achieved selective access to highly strained cyclobutene-fused scaffolds via intramolecular 4 pi electrocyclization, functionalized azetidines via an intramolecular 1,5-hydrogen atom transfer (1,5-HAT), and tricyclic adducts via an intermolecular [4 + 2] Diels-Alder cycloaddition. Comprehensive experimental and density functional theory (DFT) studies reveal that the precise pathway divergence of these photogenerated transient intermediates is strictly dictated by conformationally controlled kinetic barriers. These geometric parameters govern not only the accessibility of the highly reactive, twisted trans-cycloalkene intermediate but also the subsequent kinetic competition among divergent reaction channels. Ultimately, this work demonstrates that visible-light sensitization enables the generation and productive exploitation of such high-energy transient species, providing a modular blueprint for the programmed construction of complex architectures from simple diene precursors.

Stereoselective chemical glycosylation represents the key steps for the construction of structurally well-defined glycans and glycoconjugates, which are essential for interrogating their biological functions and developing carbohydrate-based medicines. This review highlights advances in the past two years in stereoselective O-glycosylation methodologies, including THF-modulated glycosylation, donor-derived auxiliary group-mediated glycosylation, catalyst-mediated glycosylation, and non-assisted aglycon transfer glycosylation.

A palladium-catalyzed and ligand-controlled regiodivergent intramolecular cyclization of ketone-vinylbicyclo[1.1.0]butanes (Ketone-VC-BCBs) has been developed. Using Trost-Ph-Phos as the ligand, intramolecular nucleophilic attack of the carbonyl group onto the zwitterionic palladium species followed by a proton transfer affords oxaspiro[3.4]oct-1-en-5-one derivatives in moderate yields with excellent diastereoselectivities. In contrast, employment of 1,4-bis(diphenylphosphino)butane (DPPB, L3 ) promotes intramolecular a proton migration and a rearrangement to generate a novel zwitterionic palladium species, which subsequently undergoes cyclization to deliver unexpected rearranged products as bicy-clo[3.1.1]heptanes in good yields. Ligand-controlled modulation of proton transfer pathways governs the divergent reaction outcomes, enabling the selective formation of two structurally distinct products. The proposed mechanisms were further supported by deuterium-labeling experiments and DFT calculations. The further transformation of the obtained products has also been presented. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Head-to-tail macrocyclization is a cornerstone transformation in cyclic peptide synthesis, yet its practical implementation remains constrained by extensive oligomerization under concentrated conditions. Here we report a SuFEx-enabled acyl fluoride activation strategy that intrinsically biases peptide macrocyclization toward intramolecular amide bond formation, enabling highly selective head-to-tail cyclization at concentrations up to 100 mM. In contrast to conventional uronium- and phosphonium-based coupling reagents, which generate complex oligomeric mixtures under identical conditions, the SuFEx-derived acyl fluoride pathway consistently affords cyclic monomers with minimal dimerization across diverse peptide sequences. Density functional theory calculations reveal that acyl fluoride activation reshapes the macrocyclization energy landscape by favoring irreversible ring closure while disfavoring oligomer growth, providing a mechanistic basis for the observed chemoselectivity. The method exhibits broad substrate scope, tolerating variations in ring size, sequence composition, and functionalized residues, and is readily translated to solid-phase and automated synthesis platforms. These results establish SuFEx-enabled acyl fluoride activation as a fundamentally distinct and practically robust solution to peptide macrocyclization under high-concentration conditions.

The folding of membrane protein cytoplasmic domains on the endoplasmic reticulum (ER) surface, and their coordination with transmembrane and exoplasmic regions, remains poorly understood. Through a genome-wide CRISPR-Cas9 screen, we identified the ER-anchored FK506 binding protein 8 (FKBP8) as a chaperone essential for membrane protein folding and assembly. Using ABC transporters as model substrates, we show that FKBP8 cooperates with Hsp70-Hsp90 machinery to remodel nascent or misfolded cytosolic domains into their native conformations. Cryo-EM analysis reveals that FKBP8 employs a conserved hydrophobic phi 94 phi 96 phi 97/phi 158 phi 162 cluster to help form a large client-binding cavity within the FKBP8-Hsp90 complex that captures folding intermediates. FKBP8 deficiency, disruption of this cluster, or disease-associated mutations within FKBP8 abolish substrate maturation, leading to ER retention and degradation. Reconstitution with purified components demonstrates that FKBP8 and Hsp40-Hsp70-HOP-Hsp90 constitute a minimal machinery capable of restoring the native structure of a misfolded ABC transporter. These findings uncover a dedicated folding module at the ER-cytosol interface that bridges cytosolic chaperones with membrane protein quality control, suggesting a broad role for FKBP8 in safeguarding the biogenesis of complex membrane proteins.

Loss of functional beta cells is a hallmark of diabetes, and restoring beta cell mass remains a critical goal in the quest for a specific therapy. One potential strategy is to convert non-beta cells in the islet, such as alpha cells, into insulin-producing cells. Although several compounds have been identified to induce beta cell-like features in alpha cells, none have been successfully translated into clinical applications. In this study, we identify PRC2 inhibitors as potent inducers of beta cell-enriched gene expression in alpha cells, acting through modulation of the AR-ETV1 complex. AR inhibition suppresses glycogen synthesis and enhances the pentose phosphate pathway. Direct metabolic reprogramming with methyl esterified 6-phosphogluconate, an intermediate metabolite of the pentose phosphate pathway, induces beta cell-like features in alpha cells, stimulates beta cell regeneration and ameliorates diabetes. Our findings demonstrate that metabolic reprogramming drives beta cell regeneration and highlight a promising therapeutic strategy for diabetes.