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Category Archives: Noticias
Covers 2020
This year the group has contributed with two cover:
· Chem Med Chem
Pyrrolo[1,2‐a]quinoxalines: Insulin Mimetics that Exhibit Potent and Selective Inhibition against Protein Tyrosine Phosphatase 1B
Javier García‐Marín, Mercedes Griera, Patricia Sánchez‐Alonso, Bruno Di Geronimo, Francisco Mendicuti, Manuel Rodríguez‐Puyol*, Ramón Alajarín*, Beatriz de Pascual‐Teresa, Juan J. Vaquero*, Diego Rodríguez‐Puyol*
| The Front Cover shows a C2C12 cell with the inhibitor 4‐benzylpyrrolo[1,2‐a]quinoxaline targeting the α3/α6/α7 tunnel in the Protein Tyrosine Phosphatase 1B (PTP1B) represented as a ribbon diagram. The insulin receptor (clear green) and the glucose transporter (clear yellow) shown at the cell membrane are involved in the glucose uptake by the cell. The inhibition of PTP1B by this molecule and their analogues produces an insulin mimetic effect. This is indicated by red arrows for the glucose molecules (in sticks) crossing the cell membrane to the cytosol. |
· Org Lett
Selective Synthesis of Phenanthrenes and Dihydrophenanthrenes via Gold-Catalyzed Cycloisomerization of Biphenyl Embedded Trienynes
Ana Milián, Patricia García-García*, Adrián Pérez-Redondo, Roberto Sanz, Juan J. Vaquero, and Manuel A. Fernández-Rodríguez*
| The cover art illustrates the solvent-controlled gold(I)-catalyzed selective synthesis of phenanthrenes and dihydrophenanthrenes from easily available biphenyl-embedded trienynes. Notably, the phenanthrene synthesis developed is complementary to the well-studied strategy that produces regioisomeric phenanthrenes, resulting from the competitive nucleophilic addition of biphenyl to the activated alkyne. In addition, the isolation of the cyclobutenyl derivative depicted in the figure accounts for the participation of cyclobutene species in the catalytic cycle. |
Catalysts 10.20
Gold-Catalyzed Synthetic Strategies towards Four-Carbon Ring Systems
Guillermo Otárola, Juan J. Vaquero, Estíbaliz Merino*, Manuel A. Fernández-Rodríguez*
Catalysts, 2020, Early View
DOI: 10.3390/catal10101178
| 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. |
Nefrología 10.20
The pHLIP system as a vehicle for microRNAs in the kidney
Verónica Miguel, Carlos Rey, José Luis Aceña, Francisco Maqueda, Carlos Fernández-Hernando, Diego Rodríguez-Puyol, Juan J. Vaquero, Santiago Lamas
Nefrología, 2020
DOI: 10.1016/j.nefro.2020.05.007
| 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 [low] 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. |
Org Lett 09.2020
Selective Synthesis of Phenanthrenes and Dihydrophenanthrenes via Gold-Catalyzed Cycloisomerization of Biphenyl Embedded Trienynes
Ana Milián, Patricia García-García*, Adrián Pérez-Redondo, Roberto Sanz, Juan J. Vaquero, and Manuel A. Fernández-Rodríguez*
Org. Lett, 2020, ASAP
DOI: acs.orglett.0c03067
Highlighted as Cover Picture: link
| 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. |
ChemMedChem 09.20
Pyrrolo[1,2‐a]quinoxalines: Insulin Mimetics that Exhibit Potent and Selective Inhibition against Protein Tyrosine Phosphatase 1B
Javier García‐Marín, Mercedes Griera, Patricia Sánchez‐Alonso, Bruno Di Geronimo, Francisco Mendicuti, Manuel Rodríguez‐Puyol*, Ramón Alajarín*, Beatriz de Pascual‐Teresa, Juan J. Vaquero*, Diego Rodríguez‐Puyol*
ChemMedChem, 2020, Early View
DOI: 10.1002/cmdc.202000446
Highlighted as Cover Picture: link
| 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[1,2‐a]quinoxalines 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. |
EurJOC 04.2020
Practical solvent‐free microwave‐assisted hydroboration of alkynes
Julia Altarejos, David Sucunza, Juan José Vaquero, Javier Carreras*
Eur. J. Org. Chem., 2020, Accepted Articles
DOI: 10.1002/ejoc.202000110
Highlighted in ChemistryViews: web, twitter, youtube
| 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. |
ChemComm 03.2020
Expanding the BN-embedded PAH family: 4a-aza-12a-borachrysene
Alberto Abengózar,‡ Isabel Valencia,‡ Guillermo G. Otárola, David Sucunza,* Patricia García-García, Adrián Pérez-Redondo, Francisco Mendicuti and Juan J. Vaquero*
Chem. Commun., 2020, Advance Article
DOI: 10.1039/C9CC09998K
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 (ΦF = 0.68).
Prof. Dr. Manuel Alcarazo talk, 20.02.20
Prof. Dr. Manuel Alcarazo talk
Prof. Dr. Manuel Alcarazo, Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen (Germany)
Fosfinas catiónicas y sales de sulfonio: Síntesis y aplicaciones
Sala de Grados, Edificio de Farmacia, UAH. February 20th, 17.00.
(picture)
J. Org. Chem. 12.2019
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 Garre, Raúl Losantos, Sara Gutiérrez, David Sucunza, Patricia García-García, Diego Sampedro and Juan J. Vaquero
J. Org. Chem., Article ASAP
DOI: 10.1021/acs.joc.9b02451
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 (ϕf 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 (ϕf = 0.85 in water), may be of particular importance.