The role of substituents in retro Diels-Alder extrusion of CO2 from 2(H)-pyrone cycloadducts

YesAn experimental and computational investigation is conducted into the role of substituents in retro Diels-Alder extrusion of CO2 from 2-oxa-bicyclo[2.2.2]oct-5-en-3-ones. We provide the first experimental evidence that loss of CO2 from the cycloadducts significantly depends on the nature and position of the substituents. For example, we show that whilst 5-carboethoxy-2-pyrone undergoes a more facile cycloaddition that 3-carboethoxy-2-pyrone, the cycloadduct from the latter pyrone undergoes a more facile loss of CO2 than the cycloadduct from the former pyrone.EPSRC, Yorkshire Cancer Research, Yorkshire Enterprise Fellowship

Application of small molecule FPR1 antagonists in the treatment of cancers

YesThe formylpeptide receptor-1 (FPR1) is a member of the chemotactic GPCR-7TM formyl peptide receptor family, whose principle function is in trafficking of various leukocytes into sites of bacterial infection and inflammation. More recently, FPR1 has been shown to be expressed in different types of cancer and in this context, plays a significant role in their expansion, resistance and recurrence. ICT12035 is a selective and potent (30 nM in calcium mobilisation assay) small molecule FPR1 antagonist. Here, we demonstrate the efficacy of ICT12035, in a number of 2D and 3D proliferation and invasion in vitro assays and an in vivo model. Our results demonstrate that targeting FPR1 by a selective small molecule antagonist, such as ICT12035, can provide a new avenue for the treatment of cancers

Study of the chemotactic response of multicellular spheroids in a microfluidic device

YesWe report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC–19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC–19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it.This work has been supported by National Research Program of Spain (DPI2011-28262-c04-01) and by the project "MICROANGIOTHECAN" (CIBERBBN, IMIBIC and SEOM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Iminofosforanos en química heterocíclica : nuevas reacciones de anelación de pirimidinas, piridinas, pirazoles y triazoles / María Victoria Vinader Brugarolas ; directores Pedro Molina Buendía, Antonio Arqués Adame.

Tesis-Universidad de Murcia.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. T.M.-578

Control of the stereochemistry of C14 hydroxyl during the total synthesis of withanolide E and physachenolide C

YesThe stereochemical outcome of the epoxidation of Δ14–15 cholestanes with mCPBA is controlled by the steric bulk of a C17 substituent. When the C17 is in the β configuration, the epoxide is formed in the α face, whereas if the C17 is trigonal (flat) or the substituent is in the α configuration, the epoxide is formed in the β face. The presence of a hydroxyl substituent at C20 does not influence the stereochemical outcome of the epoxidation.We thank University of Bradford for a bursary (MA)

Isolation and characterisation of all four diastereomeric intermediates from a horner-wittig reaction

The Horner-Wittig reaction between diphenyl(2-phenylpropyl)phosphine oxide and 1-naphtaldehyde affords an equal mixture of the cis and trans isomers even though the formation of the initial adduct is selective. © 2013 Copyright Taylor and Francis Group, LLC

Configuration of compounds screened against heparanase and their relationship to heparan sulfate polysaccharide backbone.

<p>Configuration of compounds screened against heparanase and their relationship to heparan sulfate polysaccharide backbone.</p

Rationale for the selectivity in the hydrogenation step for 18a-18d.

<p>Hydrogen is transferred from the surface of the catalyst to the least hindered face of the alkene shown by an arrow.</p

Compound 19.

<p>Compound 19.</p