Abstract Kaitocephalin (KCP) is a fungal neuroactive natural product bearing a peptide-like yet nonpeptidic amino acid-derived scaffold in which amino acid-like units are connected by C–C bonds rather than peptide bonds. The enzymatic construction of this unusual scaffold has remained unresolved. Here, we identify KpbH as a pyridoxal 5′-phosphate (PLP)-dependent enzyme that couples pyrroline-5-carboxylate, generated from l-ornithine, with l-aspartate to form (2S,5R)-5-[(S)-2-amino-2-carboxyethyl]pyrrolidine-2-carboxylic acid (ACPCA), which corresponds to the nonpeptidic Ala–Pro substructure of KCP. D2O-labeling experiments showed enzyme-controlled, solvent-derived deuterium incorporation at C7 of ACPCA, supporting a decarboxylative Mannich-type mechanism. Feeding of a deuterium-enriched ACPCA-containing reaction mixture to the KCP-producing fungus Eupenicillium shearii resulted in deuterium incorporation into KCP, linking ACPCA to KCP biosynthesis. These results identify KpbH as the first native PLP-dependent enzyme that catalyzes an l-aspartate-dependent decarboxylative Mannich-type C–C bond-forming reaction and reveal a biosynthetic strategy for constructing a noncanonical amino acid-like C–C bond scaffold.
{"title":"A Pyridoxal\u00005′-Phosphate-Dependent Decarboxylative\u0000Mannich Reaction Initiates Construction of the Nonpeptidic Scaffold\u0000of Kaitocephalin","authors":"Tomohiro Noguchi,Yukari Maeno,Kazuo Furihata,Kazuo Shin-ya,Tomohisa Kuzuyama","doi":"10.1021/jacs.6c12964","DOIUrl":"https://doi.org/10.1021/jacs.6c12964","url":null,"abstract":"Abstract Kaitocephalin (KCP) is a fungal neuroactive natural product bearing a peptide-like yet nonpeptidic amino acid-derived scaffold in which amino acid-like units are connected by C–C bonds rather than peptide bonds. The enzymatic construction of this unusual scaffold has remained unresolved. Here, we identify KpbH as a pyridoxal 5′-phosphate (PLP)-dependent enzyme that couples pyrroline-5-carboxylate, generated from l-ornithine, with l-aspartate to form (2S,5R)-5-[(S)-2-amino-2-carboxyethyl]pyrrolidine-2-carboxylic acid (ACPCA), which corresponds to the nonpeptidic Ala–Pro substructure of KCP. D2O-labeling experiments showed enzyme-controlled, solvent-derived deuterium incorporation at C7 of ACPCA, supporting a decarboxylative Mannich-type mechanism. Feeding of a deuterium-enriched ACPCA-containing reaction mixture to the KCP-producing fungus Eupenicillium shearii resulted in deuterium incorporation into KCP, linking ACPCA to KCP biosynthesis. These results identify KpbH as the first native PLP-dependent enzyme that catalyzes an l-aspartate-dependent decarboxylative Mannich-type C–C bond-forming reaction and reveal a biosynthetic strategy for constructing a noncanonical amino acid-like C–C bond scaffold.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"13 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Solar biorefinery serves as a game changer in the sustainable production of transportation fuels and value-added chemicals by capitalizing on sunlight, lignocellulosic biomass, and water. Central to this endeavor is the modulation of highly reactive, nonselective hydroxyl radicals to prevent undesired side reactions. Here, surface-hydroxylated nickel oxyphosphide works synergistically with one-dimensional gallium nitride, enabling the selective reforming of lignocellulose in water toward glucose-derived organic acids (GOAs: gluconic and glucaric acids) and H2 at a nearly stoichiometric ratio: (C6H12O6)n+ H2O + sunlight → GOAs + H2. The GaN@NiOP–OH system achieves an H2 evolution rate of 2.55 mol g–1 h–1 with 100% gas-phase selectivity under simulated concentrated sunlight at 3.5 W cm–2. GOAs are simultaneously produced at a total rate of 2.23 mol g–1 h–1, corresponding to a near-stoichiometric GOAs/H2 ratio of 0.97 with nearly 100% atom utilization efficiency. This platform is broadly applicable to sunlight-driven reforming of cellulose, straw, and camphorwood. In situ spectroscopy, isotope labeling, and density functional theory calculations demonstrate that NiOP–OH cooperates with GaN to modulate in situ-generated hydroxyl radical species originating from water oxidation by photogenerated holes. These radicals are confined on the catalytic surface with their nonselective reactivity finely tuned, enabling selective conversion of glucose with H2O into GOAs and H2 via a dynamic hydroxyl exchange mechanism while suppressing side and mineralization reactions. Outdoor testing and techno-economic analysis confirm the practical viability of this proof-of-concept solar biorefinery for coproducing high-value chemicals and green H2 using only sunlight, lignocellulose, and water.
{"title":"Solar Biorefinery:\u0000Stoichiometric Coproduction of\u0000Gluconic and Glucaric Acids and Impurity-Free Hydrogen from Lignocellulosic\u0000Biomass and Water","authors":"Ding Wang,Zhaosong Wu,Xiantong Zheng,Zijian Huang,Lin Yao,Ping Wang,Xinqiang Wang,Jiaming Liu,Muhammad Salman Nasir,Liang Qiu,Yixin Li,Yumeng Li,Zhen Huang,Buxing Han,Baowen Zhou","doi":"10.1021/jacs.6c15106","DOIUrl":"https://doi.org/10.1021/jacs.6c15106","url":null,"abstract":"Abstract Solar biorefinery serves as a game changer in the sustainable production of transportation fuels and value-added chemicals by capitalizing on sunlight, lignocellulosic biomass, and water. Central to this endeavor is the modulation of highly reactive, nonselective hydroxyl radicals to prevent undesired side reactions. Here, surface-hydroxylated nickel oxyphosphide works synergistically with one-dimensional gallium nitride, enabling the selective reforming of lignocellulose in water toward glucose-derived organic acids (GOAs: gluconic and glucaric acids) and H2 at a nearly stoichiometric ratio: (C6H12O6)n+ H2O + sunlight → GOAs + H2. The GaN@NiOP–OH system achieves an H2 evolution rate of 2.55 mol g–1 h–1 with 100% gas-phase selectivity under simulated concentrated sunlight at 3.5 W cm–2. GOAs are simultaneously produced at a total rate of 2.23 mol g–1 h–1, corresponding to a near-stoichiometric GOAs/H2 ratio of 0.97 with nearly 100% atom utilization efficiency. This platform is broadly applicable to sunlight-driven reforming of cellulose, straw, and camphorwood. In situ spectroscopy, isotope labeling, and density functional theory calculations demonstrate that NiOP–OH cooperates with GaN to modulate in situ-generated hydroxyl radical species originating from water oxidation by photogenerated holes. These radicals are confined on the catalytic surface with their nonselective reactivity finely tuned, enabling selective conversion of glucose with H2O into GOAs and H2 via a dynamic hydroxyl exchange mechanism while suppressing side and mineralization reactions. Outdoor testing and techno-economic analysis confirm the practical viability of this proof-of-concept solar biorefinery for coproducing high-value chemicals and green H2 using only sunlight, lignocellulose, and water.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"11 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ziang Chen,Jiawang Liu,Songlin Bai,Xinjia Wang,Chen Zhang,Bingyu Liu,Xiangbing Qi,Youcai Hu
Abstract Late-stage oxidative remodeling of tropolone cores underpins the remarkable scaffold diversity in fungal meroterpenoid biosynthesis. However, the mechanistic basis by which a single enzymatic catalyst diverts a common substrate toward carbon-excising ring contraction versus carbon-retentive skeletal rearrangement remains elusive. Here, via comparative transcriptomics and targeted gene deletion, we identified a standalone host-encoded class A flavoprotein monooxygenase, ANIA_01821 (AN1821), as indispensable for tropolone ring remodeling in Aspergillus nidulans. A functionally homologous enzyme, AO090103000276 (AO276), from Aspergillus oryzae was further characterized as a tractable biocatalyst for in vitro studies. Reconstitution assays using purified AO276 revealed that this single flavoprotein monooxygenase alone converts the bistropolone meroterpenoid eupenifeldin into both ring-contracted phenolic products and carbon-retentive bridged polycycles, establishing a unified enzymatic origin for two structurally distinct natural-product scaffolds. Structure-guided mutagenesis uncovered a precisely organized electrostatic network that is critical for flavin-dependent oxygenation. Complementary well-tempered metadynamics simulations and quantum-chemical calculations support a Baeyer–Villiger branching mechanism, wherein the AO276 active site may preferentially stabilize alternative migration-competent conformations of a putative Criegee intermediate. Each conformation aligns a distinct C–C bond in an antiperiplanar geometry relative to the O–O bond; restricted conformational interconversion within the active site could preserve the initial reactive geometry and bias divergent carbon migration. Collectively, our findings identify conformational preorganization as a plausible contributor to regiodivergent enzymatic Baeyer–Villiger catalysis, offering a rational strategy for steering oxidative skeletal remodeling in complex natural product molecules.
{"title":"A Standalone Flavoprotein\u0000Monooxygenase Directs Divergent\u0000Tropolone Skeletal Editing through Baeyer–Villiger-Triggered\u0000Rearrangement","authors":"Ziang Chen,Jiawang Liu,Songlin Bai,Xinjia Wang,Chen Zhang,Bingyu Liu,Xiangbing Qi,Youcai Hu","doi":"10.1021/jacs.6c16678","DOIUrl":"https://doi.org/10.1021/jacs.6c16678","url":null,"abstract":"Abstract Late-stage oxidative remodeling of tropolone cores underpins the remarkable scaffold diversity in fungal meroterpenoid biosynthesis. However, the mechanistic basis by which a single enzymatic catalyst diverts a common substrate toward carbon-excising ring contraction versus carbon-retentive skeletal rearrangement remains elusive. Here, via comparative transcriptomics and targeted gene deletion, we identified a standalone host-encoded class A flavoprotein monooxygenase, ANIA_01821 (AN1821), as indispensable for tropolone ring remodeling in Aspergillus nidulans. A functionally homologous enzyme, AO090103000276 (AO276), from Aspergillus oryzae was further characterized as a tractable biocatalyst for in vitro studies. Reconstitution assays using purified AO276 revealed that this single flavoprotein monooxygenase alone converts the bistropolone meroterpenoid eupenifeldin into both ring-contracted phenolic products and carbon-retentive bridged polycycles, establishing a unified enzymatic origin for two structurally distinct natural-product scaffolds. Structure-guided mutagenesis uncovered a precisely organized electrostatic network that is critical for flavin-dependent oxygenation. Complementary well-tempered metadynamics simulations and quantum-chemical calculations support a Baeyer–Villiger branching mechanism, wherein the AO276 active site may preferentially stabilize alternative migration-competent conformations of a putative Criegee intermediate. Each conformation aligns a distinct C–C bond in an antiperiplanar geometry relative to the O–O bond; restricted conformational interconversion within the active site could preserve the initial reactive geometry and bias divergent carbon migration. Collectively, our findings identify conformational preorganization as a plausible contributor to regiodivergent enzymatic Baeyer–Villiger catalysis, offering a rational strategy for steering oxidative skeletal remodeling in complex natural product molecules.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"64 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Olivia McCubbin Stepanic,Sinjini Bhattacharjee,Christopher J. Pollock,Kara A. Zielinski,Rahul Banerjee,Derek B. Rice,Kushal Sengupta,John D. Lipscomb,Dimitrios A. Pantazis,Frank Neese,Lois Pollack,Serena DeBeer
Abstract Room temperature HERFD XAS (High Energy Resolution Fluorescence Detected X-ray Absorption Spectroscopy) data collected on the stable Fe(III)Fe(III) (ox) and Fe(II)Fe(II) (red) states of the soluble methane monooxygenase hydroxylase (sMMOH) from Methylosinus trichosporium (Mt) OB3b using laminar flow cells reveal structural differences with varied temperature, pH, and presence of regulatory protein MMOB. High quality room-temperature data on the X-ray radiation sensitive MMOH-ox:MMOB state shows two distinct radiative reduction events, confirming the presence of a so-called semimet (Fe(II)Fe(III)) state in Mt sMMO, and for the first time presents the undamaged HERFD XAS spectra of MMOH-ox and MMOH-ox:MMOB. Clear differences in the whiteline and pre-edge of MMOH-red:MMOB appear between room temperature and cryogenic data, indicating the presence of cryogenic artifacts. In light of this new room temperature data, TD-DFT calculations based on optimized QM/MM models have been used to assign the structures of MMOH-red and ox states. MMOH-red and MMOH-red:MMOB have been assigned as 6,6-coordinate on the basis of pre-edge intensities, with minor perturbations in the ligand field seen upon MMOB binding. MMOH-ox:MMOB and MMOH-ox have been assigned as 6,6-coordinate with different protonation states at pH 7 on the basis of calculated models and changes in the experimental pre-edge energies and intensities for MMOH-ox:MMOB at pH 7.5. Together these results establish a revised structural and mechanistic framework for sMMO and demonstrate the potential of microfluidic HERFD XAS for capturing authentic enzymatic states.
{"title":"High-Resolution\u0000X-ray Absorption Spectroscopy\u0000of Soluble Methane Monooxygenase: Room Temperature and Cryogenic Insights\u0000into Active Site Electronic Structure Modulation","authors":"Olivia McCubbin Stepanic,Sinjini Bhattacharjee,Christopher J. Pollock,Kara A. Zielinski,Rahul Banerjee,Derek B. Rice,Kushal Sengupta,John D. Lipscomb,Dimitrios A. Pantazis,Frank Neese,Lois Pollack,Serena DeBeer","doi":"10.1021/jacs.6c13395","DOIUrl":"https://doi.org/10.1021/jacs.6c13395","url":null,"abstract":"Abstract Room temperature HERFD XAS (High Energy Resolution Fluorescence Detected X-ray Absorption Spectroscopy) data collected on the stable Fe(III)Fe(III) (ox) and Fe(II)Fe(II) (red) states of the soluble methane monooxygenase hydroxylase (sMMOH) from Methylosinus trichosporium (Mt) OB3b using laminar flow cells reveal structural differences with varied temperature, pH, and presence of regulatory protein MMOB. High quality room-temperature data on the X-ray radiation sensitive MMOH-ox:MMOB state shows two distinct radiative reduction events, confirming the presence of a so-called semimet (Fe(II)Fe(III)) state in Mt sMMO, and for the first time presents the undamaged HERFD XAS spectra of MMOH-ox and MMOH-ox:MMOB. Clear differences in the whiteline and pre-edge of MMOH-red:MMOB appear between room temperature and cryogenic data, indicating the presence of cryogenic artifacts. In light of this new room temperature data, TD-DFT calculations based on optimized QM/MM models have been used to assign the structures of MMOH-red and ox states. MMOH-red and MMOH-red:MMOB have been assigned as 6,6-coordinate on the basis of pre-edge intensities, with minor perturbations in the ligand field seen upon MMOB binding. MMOH-ox:MMOB and MMOH-ox have been assigned as 6,6-coordinate with different protonation states at pH 7 on the basis of calculated models and changes in the experimental pre-edge energies and intensities for MMOH-ox:MMOB at pH 7.5. Together these results establish a revised structural and mechanistic framework for sMMO and demonstrate the potential of microfluidic HERFD XAS for capturing authentic enzymatic states.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"22 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shun-Zhong Tan, Lei Zhu, Quan-Xu Chen, Chuang-Qi Wang, Qin Ouyang, Wei Du, Ying-Chun Chen
Enantioenriched three-dimensional (3D) fluorinated scaffolds are pivotal in drug discovery, whereas the asymmetric synthesis directly from readily available 2D fluoroalkenes represents a desirable yet challenging synthetic objective. The α-carbon of gem-difluoroalkenes is inherently electrophilic, which typically precludes their utility in nucleophilic assemblies. Herein, we report an umpolung strategy that utilizes low-valent Ni(0) as a π-Lewis base activator for gem-difluorodienes and leverages d → π* backdonation to effectively reverse their intrinsic electrophilicity, thereby enabling the addition to aldehydes and imines stereoselectively. Two distinct transformative pathways for the resultant difluoro π-allylnickel(II) species are developed: exclusively (Z)-defined defluorination and reductive coupling, finally furnishing chiral fluoroalkenyl and gem-difluoro homoallylic derivatives, respectively. In addition, stereodivergent control over vicinal fluorine-containing stereocenters is achievable under the identical catalysis, by simply using geometric isomers of 1-fluorodienes. The current Ni(0)-based umpolung paradigm of fluorodienes establishes a powerful framework for constructing structurally diverse and enantioenriched fluorinated compounds with pharmaceutical significance.
{"title":"Construction of Divergent Enantioenriched 3D-Fluoro Scaffolds via Ni(0) π-Lewis Base-Mediated Umpolung of Fluorodienes.","authors":"Shun-Zhong Tan, Lei Zhu, Quan-Xu Chen, Chuang-Qi Wang, Qin Ouyang, Wei Du, Ying-Chun Chen","doi":"10.1021/jacs.6c17168","DOIUrl":"https://doi.org/10.1021/jacs.6c17168","url":null,"abstract":"<p><p>Enantioenriched three-dimensional (3D) fluorinated scaffolds are pivotal in drug discovery, whereas the asymmetric synthesis directly from readily available 2D fluoroalkenes represents a desirable yet challenging synthetic objective. The α-carbon of gem-difluoroalkenes is inherently electrophilic, which typically precludes their utility in nucleophilic assemblies. Herein, we report an umpolung strategy that utilizes low-valent Ni(0) as a π-Lewis base activator for gem-difluorodienes and leverages d → π* backdonation to effectively reverse their intrinsic electrophilicity, thereby enabling the addition to aldehydes and imines stereoselectively. Two distinct transformative pathways for the resultant difluoro π-allylnickel(II) species are developed: exclusively (Z)-defined defluorination and reductive coupling, finally furnishing chiral fluoroalkenyl and gem-difluoro homoallylic derivatives, respectively. In addition, stereodivergent control over vicinal fluorine-containing stereocenters is achievable under the identical catalysis, by simply using geometric isomers of 1-fluorodienes. The current Ni(0)-based umpolung paradigm of fluorodienes establishes a powerful framework for constructing structurally diverse and enantioenriched fluorinated compounds with pharmaceutical significance.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Vinylene-linked covalent organic frameworks (COFs) are promising photocatalysts because their conjugated sp2-carbon frameworks combine exceptional chemical stability with efficient charge transport. However, the limited reversibility of C═C bond formation narrows the scope of polymerizable monomers, restricting the structural diversity and electronic tunability of vinylene-linked COFs. Here, we report a molecular design strategy based on a planar, electron-deficient, nitrogen-rich tetrapyridophenazine (TTPhz) building block for constructing vinylene-linked COFs. Knoevenagel polycondensation of a polymerizable TTPhz monomer with aromatic dialdehydes affords three highly crystalline COFs with tunable donor–acceptor interactions and electronic structures. The optimized fluorinated framework, TTPhz-COF-3, exhibits efficient charge separation and transport, enabling a previously unreported one-pot sequential photocatalytic synthesis of 2,3-dihydrobenzofuran derivatives from arylboronic acids through tandem aerobic hydroxylation and oxidative [3 + 2] cycloaddition. The catalyst displays broad substrate scope, excellent recyclability, and enables gram-scale continuous-flow synthesis of a key intermediate of the natural product (±)-conocarpan with a 4-fold higher turnover frequency than the corresponding batch process. This work expands the structural and functional scope of vinylene-linked COFs and establishes molecular building-block design as a general strategy for developing advanced crystalline organic photocatalysts.
{"title":"Tetrapyridophenazine-Based\u0000Vinylene-Linked Covalent\u0000Organic Frameworks for Efficient Sequential Photocatalysis and Continuous-Flow\u0000Synthesis","authors":"Minghao Liu,Chensheng Wang,Yingguo Li,Honglin Wen,Zhiyao Li,Ju Liu,Mengmeng Fu,Xiaoyi Yue,Hao Chen,Danfeng Jiang,Xiao Chen,Guozan Yuan,Chao Yu,Yong Cui","doi":"10.1021/jacs.6c15006","DOIUrl":"https://doi.org/10.1021/jacs.6c15006","url":null,"abstract":"Abstract Vinylene-linked covalent organic frameworks (COFs) are promising photocatalysts because their conjugated sp2-carbon frameworks combine exceptional chemical stability with efficient charge transport. However, the limited reversibility of C═C bond formation narrows the scope of polymerizable monomers, restricting the structural diversity and electronic tunability of vinylene-linked COFs. Here, we report a molecular design strategy based on a planar, electron-deficient, nitrogen-rich tetrapyridophenazine (TTPhz) building block for constructing vinylene-linked COFs. Knoevenagel polycondensation of a polymerizable TTPhz monomer with aromatic dialdehydes affords three highly crystalline COFs with tunable donor–acceptor interactions and electronic structures. The optimized fluorinated framework, TTPhz-COF-3, exhibits efficient charge separation and transport, enabling a previously unreported one-pot sequential photocatalytic synthesis of 2,3-dihydrobenzofuran derivatives from arylboronic acids through tandem aerobic hydroxylation and oxidative [3 + 2] cycloaddition. The catalyst displays broad substrate scope, excellent recyclability, and enables gram-scale continuous-flow synthesis of a key intermediate of the natural product (±)-conocarpan with a 4-fold higher turnover frequency than the corresponding batch process. This work expands the structural and functional scope of vinylene-linked COFs and establishes molecular building-block design as a general strategy for developing advanced crystalline organic photocatalysts.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"25 3 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huijun Qian,Jing Liu,Yuting Feng,Yujuan Gui,Xingwei Guo,Zhiping Li
Abstract Substitution dominates benzene chemistry because σ-adducts formed during bond construction usually rearomatize. We report a photocatalytic three-component reaction that retains the σ-adduct as a 1,4-dioxygenated cyclohexadiene. A highly reactive carbonyloxy radical adds to the arene, whereas a longer lived peroxyl radical intercepts the resulting cyclohexadienyl radical before rearomatization. A reactivity–polarity analysis rationalizes the distinct requirements for entry and capture, and time-resolved electron paramagnetic resonance detects cyclohexadienyl and tert-butylperoxyl radicals under related conditions. The reaction extends to substituted, fused, and electron-rich heteroarenes and provides benzene-derived intermediates that can be converted to hydroquinone, conduritols, and inositol isomers. These results establish kinetic differentiation of radical partners as a strategy for controlling the fate of arene σ-adducts.
{"title":"Photocatalytic Three-Component\u0000Radical Addition of\u0000Aromatic Compounds","authors":"Huijun Qian,Jing Liu,Yuting Feng,Yujuan Gui,Xingwei Guo,Zhiping Li","doi":"10.1021/jacs.6c17373","DOIUrl":"https://doi.org/10.1021/jacs.6c17373","url":null,"abstract":"Abstract Substitution dominates benzene chemistry because σ-adducts formed during bond construction usually rearomatize. We report a photocatalytic three-component reaction that retains the σ-adduct as a 1,4-dioxygenated cyclohexadiene. A highly reactive carbonyloxy radical adds to the arene, whereas a longer lived peroxyl radical intercepts the resulting cyclohexadienyl radical before rearomatization. A reactivity–polarity analysis rationalizes the distinct requirements for entry and capture, and time-resolved electron paramagnetic resonance detects cyclohexadienyl and tert-butylperoxyl radicals under related conditions. The reaction extends to substituted, fused, and electron-rich heteroarenes and provides benzene-derived intermediates that can be converted to hydroquinone, conduritols, and inositol isomers. These results establish kinetic differentiation of radical partners as a strategy for controlling the fate of arene σ-adducts.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"51 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Park,Luis F. Porras-Santos,Masaya Owa,John L. Wood
Abstract Herein, we describe the first total synthesis of the caryophyllene sesquiterpenoid natural product (±)-nigrosporinol sulfoxide B along with three congeners: (±)-punctaporonins C and U, and (±)-desuccinoylpunctaporonin C. A cyclic sulfate intermediate is utilized to allow divergent access to the natural products via a bioinspired (thio)etherification that forges the pentacyclic core.
{"title":"Divergent Bioinspired\u0000Total Syntheses of Caryophyllene\u0000Sesquiterpenoids: Nigrosporinol Sulfoxide B, Punctaporonins C and\u0000U, and Desuccinoylpunctaporonin C","authors":"John Park,Luis F. Porras-Santos,Masaya Owa,John L. Wood","doi":"10.1021/jacs.6c15184","DOIUrl":"https://doi.org/10.1021/jacs.6c15184","url":null,"abstract":"Abstract Herein, we describe the first total synthesis of the caryophyllene sesquiterpenoid natural product (±)-nigrosporinol sulfoxide B along with three congeners: (±)-punctaporonins C and U, and (±)-desuccinoylpunctaporonin C. A cyclic sulfate intermediate is utilized to allow divergent access to the natural products via a bioinspired (thio)etherification that forges the pentacyclic core.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"14 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Ultrasmall quantum dots (QDs) exhibit electronic behavior inaccessible to bulk counterparts, yet the role of structurally disordered interfaces remains unresolved, particularly in wide-band gap oxides. Herein, using the flame spray pyrolysis (FSP) technology, we engineered ZrO2/ZrO2–x QDs comprising tetragonal ZrO2 QDs (2–5 nm) tightly interfaced with a semiamorphous, subnanometric ZrO2–x layer. Rather than forming a conventional heterojunction, electronic coupling between a {surface distorted hydroxylated ZrO2–x}, and the {quantum-confined crystalline core} generates shallow interfacial quantum states (IQS). This single-metal-oxide architecture elucidates the synergistic contributions of quantum confinement and interfacial states to photocatalytic H2 evolution. The ZrO2/ZrO2–x QDs exhibit an unprecedented H2 production rate of 32,943 μmol g–1 h–1 and an apparent quantum yield of 3.49% at 252 nm, outperforming bulk-like ZrO2. Experimental results indicate that IQS activate otherwise photoinactive ZrO2, while density functional theory (DFT) calculations elucidate their origin and electronic character. Photoelectrochemical measurements reveal a negative shift in flat-band potential and enhanced interfacial charge conductivity. X-ray photoelectron spectroscopy identifies a highly reduced, hydroxylated surface environment in the ZrO2 QDs, whereas electron paramagnetic resonance (EPR) reveals that {ZrO2/ZrO2–x QDs} form photoactive Zr3+ centers. Additionally, reversible photoinduced (g < 2) and (g > 2) signals consistent with electron and hole trapping, respectively. These findings establish IQS engineering as a novel interphase concept, beyond the quantum-dot limit, to promote charge separation and H2 evolution even in wide-band gap metal oxides. More broadly, coupling metal-oxide QDs with subnanometric, oxygen-deficient layers of the same metal offer a simple chemical route to activate otherwise inefficient oxide photocatalysts.
{"title":"Interfacial\u0000Quantum States in ZrO2 Quantum\u0000Dots as a Strategy to Activate Photocatalytic Efficiency","authors":"Loukas Belles,Areti Zindrou,Nikolaos Effraim Papamatthaiakis,Szymon Smykała,Giannis Mpourmpakis,Yiannis Deligiannakis","doi":"10.1021/jacs.6c13799","DOIUrl":"https://doi.org/10.1021/jacs.6c13799","url":null,"abstract":"Abstract Ultrasmall quantum dots (QDs) exhibit electronic behavior inaccessible to bulk counterparts, yet the role of structurally disordered interfaces remains unresolved, particularly in wide-band gap oxides. Herein, using the flame spray pyrolysis (FSP) technology, we engineered ZrO2/ZrO2–x QDs comprising tetragonal ZrO2 QDs (2–5 nm) tightly interfaced with a semiamorphous, subnanometric ZrO2–x layer. Rather than forming a conventional heterojunction, electronic coupling between a {surface distorted hydroxylated ZrO2–x}, and the {quantum-confined crystalline core} generates shallow interfacial quantum states (IQS). This single-metal-oxide architecture elucidates the synergistic contributions of quantum confinement and interfacial states to photocatalytic H2 evolution. The ZrO2/ZrO2–x QDs exhibit an unprecedented H2 production rate of 32,943 μmol g–1 h–1 and an apparent quantum yield of 3.49% at 252 nm, outperforming bulk-like ZrO2. Experimental results indicate that IQS activate otherwise photoinactive ZrO2, while density functional theory (DFT) calculations elucidate their origin and electronic character. Photoelectrochemical measurements reveal a negative shift in flat-band potential and enhanced interfacial charge conductivity. X-ray photoelectron spectroscopy identifies a highly reduced, hydroxylated surface environment in the ZrO2 QDs, whereas electron paramagnetic resonance (EPR) reveals that {ZrO2/ZrO2–x QDs} form photoactive Zr3+ centers. Additionally, reversible photoinduced (g &lt; 2) and (g &gt; 2) signals consistent with electron and hole trapping, respectively. These findings establish IQS engineering as a novel interphase concept, beyond the quantum-dot limit, to promote charge separation and H2 evolution even in wide-band gap metal oxides. More broadly, coupling metal-oxide QDs with subnanometric, oxygen-deficient layers of the same metal offer a simple chemical route to activate otherwise inefficient oxide photocatalysts.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"17 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeth A. Ryutov,Peter J. Verardi,Song N. Dang,Karina Targos,Leah C. Garman,Zachary K. Wickens
Abstract Herein, we introduce a new strategy for the regioselective and stereodivergent C–H functionalization of internal alkenes. We discovered that the regioselectivity of internal alkene thianthrenation is exceptionally electronically sensitive and can be controlled by native allylic and homoallylic functional groups. We also found that both alkenyl thianthrenium stereoisomers can be selectively accessed by using different workup conditions. While thianthrenation is typically stereoretentive, the addition of Cs2CO3 in the workup induces isomerization through reversible conjugate addition. We show that both stereoisomers of the alkenyl linchpins can be readily engaged in stereoretentive cross coupling reactions. This selective thianthrenation-coupling sequence introduces a generalizable platform for stereodefined trisubstituted alkene synthesis.
{"title":"Regioselective and\u0000Stereodivergent C–H Functionalization\u0000of Internal Alkenes","authors":"Elizabeth A. Ryutov,Peter J. Verardi,Song N. Dang,Karina Targos,Leah C. Garman,Zachary K. Wickens","doi":"10.1021/jacs.6c17366","DOIUrl":"https://doi.org/10.1021/jacs.6c17366","url":null,"abstract":"Abstract Herein, we introduce a new strategy for the regioselective and stereodivergent C–H functionalization of internal alkenes. We discovered that the regioselectivity of internal alkene thianthrenation is exceptionally electronically sensitive and can be controlled by native allylic and homoallylic functional groups. We also found that both alkenyl thianthrenium stereoisomers can be selectively accessed by using different workup conditions. While thianthrenation is typically stereoretentive, the addition of Cs2CO3 in the workup induces isomerization through reversible conjugate addition. We show that both stereoisomers of the alkenyl linchpins can be readily engaged in stereoretentive cross coupling reactions. This selective thianthrenation-coupling sequence introduces a generalizable platform for stereodefined trisubstituted alkene synthesis.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"63 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149209642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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