Publications > Torres-Oya et al
Synthesis of 3,4-Dihydroquinazolinones via Base-Promoted Formal [4 + 2] Cycloadditions.
Palabras clave: 3,4-dihydroquinazolinones; [4 + 2] cycloadditions; aza-ortho-quinone methides; isocyanates
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Category Archives: Publicación
Morales-Ortega et al. Chem Sci. ;:11413-11418. Visible-light-initiated metal-free C(sp(3)) -C(sp(3)) to C(sp(3)) -N conversion in homobenzylic sulfonamides with N-iodoimides.
Publications > Morales-Ortega et al
Visible-light-initiated metal-free C(sp(3)) -C(sp(3)) to C(sp(3)) -N conversion in homobenzylic sulfonamides with N-iodoimides.
1. Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química "Andrés M. del Río" (IQAR), Universidad de Alcalá Alcalá de Henares Madrid 28805 Spain. 2. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) Madrid 28034 Spain.
a. javier.carreras@uah.es
Abstract
We report a simple protocol for the transformation of C(sp(3)) -C(sp(3)) to C(sp(3)) -N in homobenzylic sulfonamides in combination with N-iodoimides to form gem-diamino derivatives. The reaction exhibits a wide functional group tolerance and allows the incorporation of bioactive-derived fragments. The mechanistic insights provided by control experiments and DFT calculations suggest that an imine intermediate is formed after C-C bond cleavage.
Humanes et al. Advanced Synthesis & Catalysis. 2025;367(12):e202500244. Synthesis of Polysubstituted Naphthalenes via Metal-Free Borylative Cyclization of o-Alkynylstyrenes.
Synthesis of Polysubstituted Naphthalenes via Metal-Free Borylative Cyclization of o-Alkynylstyrenes.
Palabras clave: boron; cyclization; enynes; naphthalene; synthetic methods
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Mañas and. Advanced Synthesis & Catalysis. 2025;367(1):e202400990. Combined Gold and Photoredox Catalysis: Synthesis of 3-Alkenyl-2H-Indazoles from 2-Alkynylazobenzenes.
Combined Gold and Photoredox Catalysis: Synthesis of 3-Alkenyl-2H-Indazoles from 2-Alkynylazobenzenes.
Palabras clave: 2-Alkynylazobenzenes; 3-Alkenyl-2H-indazoles; Gold; Hydroamination; Photoredox catalysis
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Maqueda-Zelaya et al. Arch Pharm (Weinheim). 2025;358(1):e2400614. Identification and study of new NF-κB-inducing kinase ligands derived from the imidazolone scaffold.
Publications > Maqueda-Zelaya et al
Identification and study of new NF-κB-inducing kinase ligands derived from the imidazolone scaffold.
1. Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química "Andrés M. Del Río" (IQAR), Universidad de Alcalá (IRYCIS), Alcalá de Henares, Madrid, Spain. 2. Departamento de Nefrología e Hipertensión, IIS-Fundación Jiménez Díaz UAM, Madrid, Spain. 3. RICORS2040, Madrid, Spain.
Keywords: MAP3K14; NF‐κB‐inducing kinase; NIK; imidazolone; noncanonical pathway
Abstract
Chronic kidney disease (CKD) is a growing health concern, projected to be a major cause of death by 2040, due to an increasing risk of acute kidney injury (AKI). Systems biology-derived data suggest that the unmet need for an orally available drug to treat AKI and improve CKD outcomes may be addressed by targeting kidney inflammation and, specifically, nuclear factor κB-inducing kinase (NIK), a key signaling molecule that activates the noncanonical nuclear factor κB (NF-κB) pathway. We have prepared and identified a small family of imidazolone derivatives that bind NIK and inhibit the noncanonical NF-κB activation pathway. The introduction of heterocyclic substituents in position 2 of the imidazolone core provides compounds with affinity against human NIK. Three candidates, with best affinity profile, were tested in phenotypic experiments of noncanonical NF-κB activation, confirming that the derivative bearing the 4-pyridyl ring can inhibit the processing of NFκB p100 to NFkB2 p52, which is NIK-dependent in cultured kidney tubular cells. Finally, exhaustive docking calculations combined with molecular dynamics studies led us to propose a theoretical binding mode and rationalize affinity measures, in which the aminopyridine motif is a key anchoring point to the hinge region thanks to several hydrogen bonds and the interaction of heterocyclic rings in position 2 with Ser476 and Lys482. Our result will pave the way for the development of potential drug candidates targeting NIK in the context of CKD.
Martínez-Laguna et al. J Am Chem Soc. 2024;146(49):34014-34022. Alkanes C(1)-C(6) C-H Bond Activation via a Barrierless Potential Energy Path: Trifluoromethyl Carbenes Enhance Primary C-H Bond Functionalization.
Publications > Martínez-Laguna et al
Alkanes C(1)-C(6) C-H Bond Activation via a Barrierless Potential Energy Path: Trifluoromethyl Carbenes Enhance Primary C-H Bond Functionalization.
1. Departamento de Química and Laboratorio de Catálisis Homogénea, Unidad Asociada al CSIC, CIQSO-Centro de Investigación en Química Sostenible, Universidad de Huelva, Huelva 21007, Spain. 2. Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química "Andrés M. del Río" (IQAR), Universidad de Alcalá, Alcalá de Henares, Madrid 28805, Spain. 3. The Barcelona Institute of Science and Technology, Institute of Chemical Research of Catalonia (ICIQ-CERCA), Avgda. Països Catalans, 16, Tarragona 43007, Spain. 4. Departament de Química, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain.
Abstract
In this mixed computational and experimental study, we report a catalytic system for alkane C(1)-C(6) functionalization in which the responsible step for C-H bond activation shows no barrier in the potential energy path. DFT modeling of three silver-based catalysts and four diazo compounds led to the conclusion that the Tp(F)Ag═C(H)CF(3) (Tp(F) = fluorinated trispyrazolylborate ligand) carbene intermediates interact with methane without a barrier in the potential energy surface, a prediction validated by experimentation using N(2)═C(H)CF(3) as the carbene source. The array of alkanes from propane to n-hexane led to the preferential functionalization of the primary sites with unprecedented values of selectivity for an acceptor diazo compound. The lack of those barriers implies that selectivity can no longer be controlled by differences in the energy barriers. Molecular dynamics calculations (with propane as the model alkane) are consistent with the preferential functionalization of the primary sites due to a higher concentration of such C-H bonds in the vicinity of the carbenic carbon atom.
Mañas et al. J Org Chem. 2024;89(22):16883-16888. Copper-Catalyzed Hydroamination of 2-Alkynylazobenzenes: Synthesis of 3-Alkenyl-2H-Indazoles.
Copper-Catalyzed Hydroamination of 2-Alkynylazobenzenes: Synthesis of 3-Alkenyl-2H-Indazoles.
1. Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Andrés M. del Río (IQAR), Facultad de Farmacia, Universidad de Alcalá, Alcalá de Henares, 28805 Madrid, Spain. 2. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Ctra. De Colmenar Viejo, Km. 9.100, 28034 Madrid, Spain.
Abstract
A copper-catalyzed intramolecular synthesis of 3-alkenyl-2H-indazoles from 2-alkynylazobenzenes is described. The reaction proceeds in a single step via C-N bond formation and a subsequent 1,2-hydride shift, affording products in high yields. DFT calculations suggest the 1,2-hydride shift as the rate-determining step. Further derivatization enables functionalization of the 3-alkenyl-2H-indazoles.
Mañas et al Org. Chem. Front. 2024 ;11(24):6974 -6988. Shaping cycles with light: a regiodivergent approach to tetracyclic aza-aromatic compounds.
Shaping cycles with light: a regiodivergent approach to tetracyclic aza-aromatic compounds.
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Lerma-Berlanga et al. ChemCatChem. 2024;16(23):e202400909. Au Clusters Catalyze The Disulfide Metathesis Reaction By A Reductive Addition-Oxidative Elimination Mechanism.
Publications > Lerma-Berlanga et al
Au Clusters Catalyze The Disulfide Metathesis Reaction By A Reductive Addition-Oxidative Elimination Mechanism.
Palabras clave: Oxidative addition-reductive elimination (OARE) mechanism; Disulfide metathesis; Au cluster; Computational studies; Reusable catalyst
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Humanes et al. Org Lett. 2024;26(31):6568-6573. Selective Synthesis of Boron-Functionalized Indenes and Benzofulvenes by BCl(3)-Promoted Cyclizations of ortho-Alkynylstyrenes.
Selective Synthesis of Boron-Functionalized Indenes and Benzofulvenes by BCl(3)-Promoted Cyclizations of ortho-Alkynylstyrenes.
1. Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química "Andrés M. del Río" (IQAR), Universidad de Alcalá (IRYCIS), 28805 Alcalá de Henares, Madrid, Spain. 2. Área de Química Orgánica, Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Pza. Misael Bañuelos s/n, 09001 Burgos, Spain.
Abstract
A selective, metal-free synthesis of boron-functionalized indenes and benzofulvenes via BCl(3)-mediated cyclization of o-alkynylstyrenes is described. The method allows precise control over product formation by adjusting reaction conditions. These borylated products were utilized in diverse C-B bond derivatizations and in the total synthesis of Sulindac, a nonsteroidal anti-inflammatory drug, demonstrating the versatility and practicality of the developed methodology for synthetic applications.