Category Archives: Publicación

2020, Au, Publicación

Milián et al. Org Lett. 2020;22(21):8464-8469. Selective Synthesis of Phenanthrenes and Dihydrophenanthrenes via Gold-Catalyzed Cycloisomerization of Biphenyl Embedded Trienynes.

Publications > Milián et al

Org Lett. 2020, 22, 8464

Selective Synthesis of Phenanthrenes and Dihydrophenanthrenes via Gold-Catalyzed Cycloisomerization of Biphenyl Embedded Trienynes.

Ana Milián1, Patricia García-García1, Adrián Pérez-Redondo1, Roberto Sanz2, Juan J Vaquero1, Manuel A Fernández-Rodríguez1

1. Departamento de Quı́mica Orgánica y Quı́mica Inorgánica, Instituto de Investigación Quı́mica "Andrés M. del Rı́o" (IQAR). Universidad de Alcalá (IRYCIS). Campus Cientı́fico-Tecnológico, Facultad de Farmacia, Autovía A-II, Km 33.1, 28805 Alcalá de Henares, Madrid, Spain.  2. Área de Quı́mica Orgánica, Departamento de Quı́mica, Facultad de Ciencias, Universidad de Burgos, Pza. Misael Bañuelos s/n, 09001 Burgos, Spain.

Abstract

Readily available o'-alkenyl-o-alkynylbiaryls, a particular type of 1,7-enynes, undergo a selective cycloisomerization reaction in the presence of a gold(I) catalyst to give interesting phenanthrene and dihydrophenanthrene derivatives in high yields. The solvent used provokes a switch in the evolution of the gold intermediate and plays a key role in the reaction outcome.

2020, Au, Publicación

Otarola et al. Catalysts. 2020;22(21):1178. Gold-Catalyzed Synthetic Strategies towards Four-Carbon Ring Systems.

Publications > Otarola et al

Catalysts 2020, 22, 1178

Gold-Catalyzed Synthetic Strategies towards Four-Carbon Ring Systems.

Guillermo G Otarola, Juan J Vaquero, Estíbaliz Merino, Manuel A Fernández-Rodríguez

Departamento de Quı́mica Orgánica y Quı́mica Inorgánica, Instituto de Investigación Quı́mica "Andrés M. del Rı́o" (IQAR). Universidad de Alcalá (IRYCIS). Campus Cientı́fico-Tecnológico, Facultad de Farmacia, Autovía A-II, Km 33.1, 28805 Alcalá de Henares, Madrid, Spain.

Abstract

Four carbon ring systems are frequently present in natural products with remarkable biological activities such as terpenoids, alkaloids, and steroids. The development of new strategies for the assembly of these structures in a rapid and efficient manner has attracted the interest of synthetic chemists for a long time. The current research is focused mainly on the development of synthetic methods that can be performed under mild reaction conditions with a high tolerance to functional groups. In recent years, gold complexes have turned into excellent candidates for this aim, owing to their high reactivity, and are thus capable of promoting a wide range of transformations under mild conditions. Their remarkable efficiency has been thoroughly demonstrated in the synthesis of complex organic molecules from simple starting materials. This review summarizes the main synthetic strategies described for gold-catalyzed four-carbon ring formation, as well as their application in the synthesis of natural products.

2020, Publicación

García-Marín et al. ChemMedChem. 2020;15(19):1788-1801. Pyrrolo[1,2-a]quinoxalines: Insulin Mimetics that Exhibit Potent and Selective Inhibition against Protein Tyrosine Phosphatase 1B

Publications > García-Marín et al

ChemMedChem 2020, 15, 1788 PubMed 32909701

Pyrrolo%@5B1,2-a%@5Dquinoxalines: Insulin Mimetics that Exhibit Potent and Selective Inhibition against Protein Tyrosine Phosphatase 1B.

Javier García-Marín1, Mercedes Griera2, Patricia Sánchez-Alonso3, Bruno Di Geronimo2, Francisco Mendicuti4, Manuel Rodríguez-Puyol1, Ramón Alajarín5, Beatriz de Pascual-Teresa6, Juan J Vaquero3, Diego Rodríguez-Puyol2

1. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28805, Alcalá de Henares, Spain.  2. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Ctra. Colmenar Viejo, km. 9100, 28034, Madrid, Spain.  3. Instituto de Investigación Química Andrés M. del Río, Facultad de Farmacia, Universidad de Alcalá, 28805, Alcalá de Henares, Spain.  4. Departamento de Biología de Sistemas, Universidad de Alcalá, 28805, Alcalá de Henares, Spain.  5. Departamento de Química y Bioquímica, Facultad de Farmacia, Universidad San Pablo CEU, 28925, Alcorcón, Spain.  6. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, 28805, Alcalá de Henares, Spain.

Keywords: PTP1B; biological activity; inhibitors; insulin mimetics; pyrrolo%@5B1,2-a%@5Dquinoxaline

Abstract

PTP1B dephosphorylates insulin receptor and substrates to modulate glucose metabolism. This enzyme is a validated therapeutic target for type 2 diabetes, but no current drug candidates have completed clinical trials. Pyrrolo%@5B1,2-a%@5Dquinoxalines substituted at positions C1-C4 and/or C7-C8 were found to be nontoxic to cells and good inhibitors in the low- to sub-micromolar range, with the 4-benzyl derivative being the most potent inhibitor (0.24 μm). Some analogues bearing chlorine atoms at C7 and/or C8 kept potency and showed good selectivity compared to TCPTP (selectivity index >40). The most potent inhibitors behaved as insulin mimetics by increasing glucose uptake. The 4-benzyl derivative inhibited insulin receptor substrate 1 and AKT phosphorylation. Molecular docking and molecular dynamics simulations supported a putative binding mode for these compounds to the allosteric α3/α6/α7 pocket, but inconsistent results in enzyme inhibition kinetics were obtained due to the high tendency of these inhibitors to form stable aggregates. Computational calculations supported the druggability of inhibitors.

2020, Publicación, Renal

Miguel et al. Nefrologia. 2020;:. The pHLIP system as a vehicle for microRNAs in the kidney.

Publications > Miguel et al

Nefrologia. 2020, 40, 491

The pHLIP system as a vehicle for microRNAs in the kidney.

Verónica Miguel1, a, Carlos Rey2, José Luis Aceña3, Francisco Maqueda3, Carlos Fernández-Hernando4, Diego Rodríguez-Puyol5, Juan J Vaquero3, Santiago Lamas2

1. Programa de Procesos Fisiológicos y Patológicos, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, España. Electronic address:.  2. Programa de Procesos Fisiológicos y Patológicos, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, España.  3. Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química Andrés M. del Río (IQAR), Universidad de Alcalá, IRYCIS, Alcalá de Henares, Madrid, España.  4. Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, Estados Unidos.  5. Department of Medicine and Medical Specialties, Research Foundation of the University Hospital Príncipe de Asturias, IRYCIS, Alcalá University, Alcalá de Henares, Madrid, España.

a. vmiguel@cbm.csic.es

Palabras clave: Fibrosis renal; PNA; PNAs; Renal fibrosis; miRNA; miRNAs; pHLIP

Resumen

MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene expression through post-transcriptional repression of their target messenger RNAs. A study of changes in expression of certain miRNAs in the kidney has supplied evidence on their pathogenic role and therapeutic potential in nephrology. This review proposes a nanotechnology approach based on the binding of analogs or inhibitors of miRNAs formed by peptide nucleic acids (PNAs) to peptides with a transmembrane structure sensitive to a low pH, called pHLIPs (pH %@5Blow%@5D insertion peptides). The review draws on the concept that an acidic pH in the microenvironment of the renal tubule may facilitate concentration and distribution of the pHLIP-PNA complex in this organ. In this context, we have demonstrated for the first time that targeted administration of miR-33 inhibitors with the pHLIP system effectively prevents the development of renal fibrosis, thus opening up this technology to new strategies for diagnosis and treatment of kidney diseases.

2020, Publicación

Altarejos et al. Eur J Org Chem. 2020:3024-3029. Practical Solvent-Free Microwave-Assisted Hydroboration of Alkynes

Publications > Altarejos et al

Eur. J. Org. Chem. 2020, 3024

Practical Solvent-Free Microwave-Assisted Hydroboration of Alkynes.

Julia Altarejos, David Sucunza, Juan J Vaquero, Javier Carreras

Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química “Andrés M. del Río” (IQAR), Universidad de Alcalá, IRYCIS, 28805 Madrid, Alcalá de Henares, Spain.

. javier.carreras@uah.es

Abstract

A simple and rapid protocol for the anti-Markovnikov hydroboration of alkynes assisted by microwave irradiation has been developed. Pinacolborane smoothly reacts with terminal alkynes to obtain (E)-alkenyl boronates in good yields and short reactions times in the absence of solvent. Further transformations on the carbon-boron bond of the adducts can be sequentially achieved without the need of purifying the alkenyl boronates.

2020, AzaBN, Publicación

Abengozar et al. Chem Commun (Camb). 2020;56(25):3669-3672. Expanding the BN-embedded PAH family: 4a-aza-12a-borachrysene.

Publications > Abengozar et al

Chem Commun 2020, 56, 3669 PubMed 32115593

Expanding the BN-embedded PAH family: 4a-aza-12a-borachrysene.

Alberto Abengozara, Isabel Valencia, Guillermo G Otarola, David Sucunza, Patricia Garcia-Garcia, Adrian Perez-Redondo, Francisco Mendicuti, Juan J Vaquero

Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR), Universidad de Alcala, IRYCIS, 28805 Alcala de Henares, Spain.

a. david.sucunza@uah.es, juanjose.vaquero@uah.es

Abstract

Previously unknown 4a-aza-12a-borachrysene has been synthesized in only four steps. The reactions of this BN-embedded PAH with bromine and organolithium compounds proceed with complete regioselectivity, resulting in the formation of nine derivatives. One of these, a phenylalkynyl-substituted derivative, exhibits a remarkably high fluorescence quantum yield (PhiF = 0.68).

2020, BioImag, Publicación

Garre et al. J Org Chem. 2020;85(2):441-448. Synthesis and Photophysical Behavior of a Highly Fluorescent Family of Unsymmetrical Organoboron Complexes Containing 5-(Pyridin-2-ylmethylene)imidazolidine-2,4-dione Moieties.

Publications > Garre et al

J Org Chem. 2020, 85, 441 PubMed 31858801

Synthesis and Photophysical Behavior of a Highly Fluorescent Family of Unsymmetrical Organoboron Complexes Containing 5-(Pyridin-2-ylmethylene)imidazolidine-2,4-dione Moieties.

M Soledad Garre1, Raul Losantos2, Sara Gutierrez1, David Sucunza1, Patricia Garcia-Garcia1, Diego Sampedro2, Juan J Vaquero1

1. Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala, IRYCIS , 28805 Alcala de Henares , Spain.  2. Departamento de Quimica, Centro de Investigacion en Sintesis Quimica (CISQ) , Universidad de La Rioja , Madre de Dios 53 , 26006 Logrono , Spain.

Abstract

A new and highly fluorescent family of unsymmetrical organoboron complexes containing 5-(pyridin-2-ylmethylene)imidazolidine-2,4-dione moieties has been synthesized in three steps. These compounds show strong absorptions covering a wide range of the UV-vis spectrum and are strongly emissive (varphif of up to 0.92 in CH3CN). Moreover, two fluorophores that include an alkyne or an azide group at the end of the alkyl chain and with potential utility in bioorthogonal chemistry have been developed. One of these, in which the glycol substituent provides an enhanced water solubility without compromising the fluorescence (varphif = 0.85 in water), may be of particular importance.