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.
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.
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.
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*
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.
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.
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*
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, 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.
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
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.
Dr. Abraham Mendoza, Stockholm University (Sweden) Asymmetric synthesis with chiral carbon-atom precursors
Sala de Grados, Edificio de Farmacia, UAH. October 24th, 17.00.
