Transition-Metal-Free Continuous-Flow Synthesis of 2,5-Diaryl Furans: Access to Medicinal Building Blocks and Optoelectronic Materials.

The direct transformation of 1,3-dienes into valuable 2,5-diarylfurans using transition-metal-free conditions is presented. By employing a simple oxidation─dehydration sequence on readily accessible 1,3-dienes, important 2,5-diarylfuran building blocks frequently used in medicinal and material chemistry are prepared. The oxidation step is realized using singlet oxygen, and the intermediate endoperoxide is dehydrated under metal-free conditions and at ambient temperature using the Appel reagent.

Indium-Mediated 2-Oxonia Cope Rearrangement of 1,4-Dienols to 1,3-Dienols.

An indium-mediated isomerization of 1,4-dienols to 1,3-dienols is described. This procedure consists of the addition of pentadienylindium, in a protic solvent, to aldehydes giving the kinetic γ-allylation product in high yields. The subsequent conversion of this γ-allylation product to its thermodynamic 1,3-dienol α-isomer can be achieved by its exposure to indium triflate in the presence of a substoichiometric amount of aldehyde at room temperature.

Total Synthesis of the Tetrasubstituted Furan Fatty Acid Metabolite CeDFP via Au-Catalyzed Intermolecular Alkyne Hydroarylation.

The first total synthesis of the tetrasubstituted furan fatty acid (FFA) metabolite 5-[(1 E)-2-carboxyethenyl]-3,4-dimethyl-2-furanpentanoic acid (CeDFP) is reported. CeDFP is a FFA metabolite isolated from shark livers and is related to the known FFA metabolites CMPF and CMPentylF. Key elements of the synthetic route to CeDFP include an iodine-promoted 5- endo- dig cyclization of a 1,2-alkyne diol, a methyllithium-mediated insertion of the C-methyl group, and a Au(I)-catalyzed intermolecular hydroarylation to introduce the unsaturated ester.

Resolvin E1 (R E ) attenuates LPS induced inflammation and subsequent atrophy in C2C12 myotubes.

Resolution of inflammation is now known to be an active process which in part is instigated and controlled by specialized pro-resolving lipid mediators (SPM's) derived from dietary omega-3 fatty acids. Resolvin E1 (R E ) is one of these SPM's derived from the omega-3 fatty acid eicosapentaenoic acid. Using both molecular and phenotypic functional measures we report that in a model of Lipopolysaccharide (LPS) induced inflammation, R E attenuated mRNA levels of both interlukin-6 and monocyte chemoattractant protein-1 whilst having no effect on tumor necrosis factor-α or interlukin-1β in C2C12 skeletal muscle myotubes.

A biosynthetically inspired route to substituted furans using the Appel reaction: total synthesis of the furan fatty acid F.

Appel reaction conditions have been harnessed to affect a mild biosynthetically inspired dehydration of endoperoxides to deliver multi-substituted electron rich furans. Unlike traditional dehydrative procedures, this method is metal and acid free, and can be achieved under redox neutral conditions. It is general for a range of aryl and alkyl substituted endoperoxides, and is functional group tolerant.

A mild Lewis acid mediated epoxy-ester to bicyclic ortho ester rearrangement.

A high yielding rearrangement of epoxy-esters, under Lewis acid conditions, to give bicyclic ortho esters is reported.

Preparation of highly substituted tetrahydropyrans via a metal assisted dipolar cycloaddition reaction.

A range of highly substituted tetrahydropyrans have been prepared by reaction of a donor-acceptor cyclobutane, where the donor is a metal-alkyne complex, with an aldehyde under Lewis acid conditions.

Enhancing pathways into care (EPIC): community development working with the Pakistani community to improve patient pathways within a crisis resolution and home treatment service.

Black and Minority Ethnic (BME) communities receive different pathways into mental health care with BME service users often presenting in crisis. This is associated with both an over representation of such groups in psychiatric wards and people avoiding mainstream services altogether. The Sheffield Crisis Resolution Home Treatment (CRHT) created the Enhancing Pathways Into Care (EPIC) project, which initially focused on engagement with the Pakistani community (the largest BME group in Sheffield).

A dedicated translation factor controls the synthesis of the global regulator Fis.

: (2004) 3375–3385. doi:10.1038/sj.

Mechanistic insights into the inhibition of prostate specific antigen by beta-lactam class compounds.

Prostate Specific Antigen (PSA) is a biomarker used in the diagnosis of prostate cancer and to monitor therapeutic response. However, its precise role in prostate carcinogenesis and metastasis remains largely unknown. A number of studies arguing in the favor of an active role of PSA in prostate cancer development and progression have implicated this serine protease in the release and activation of growth factors such as insulin-like growth factor 1 (IGF1) through cleavage of insulin like growth factor binding protein 3 and Transforming Growth Factor beta (TGF-beta) through cleavage of Latent TGF-beta.

Novel formation and use of a Nicholas carbocation in the synthesis of highly substituted tetrahydrofurans.

The first formation of a Nicholas carbocation through cleavage of a carbon-carbon sigma bond has allowed the preparation of highly substituted tetrahydrofurans in a formal dipolar cycloaddition reaction.

A dedicated translation factor controls the synthesis of the global regulator Fis.

BipA is a highly conserved protein with global regulatory properties in Escherichia coli. We show here that it functions as a translation factor that is required specifically for the expression of the transcriptional modulator Fis. BipA binds to ribosomes at a site that coincides with that of elongation factor G and has a GTPase activity that is sensitive to high GDP:GTP ratios and stimulated by 70S ribosomes programmed with mRNA and aminoacylated tRNAs.

An unusual oxidative cyclization: studies towards the biomimetic synthesis of pyridomacrolidin.

An unusual oxidative cyclization of a N-hydroxy pyridone 9 with Z-2-cyclodecenone 11 has been achieved, thus demonstrating a possible biomimetic route to pyridomacrolidin 2. [reaction: see text]

Prostate-specific antigen (PSA)-mediated proliferation, androgenic regulation and inhibitory effects of LY312340 in HOS-TE85 (TE85) human osteosarcoma cells.

Background: PSA mediates growth factor responses that stimulate proliferation of prostatic and other cellular types. Androgen-sensitive TE85 human osteosarcoma cells were used to study PSA as a potential mediator of prostatic cancer growth and osseous metastasis.

Materials And Methods: TE85 cells were probed for PSA mRNA and protein levels under testosterone (T)-replete and--depleted conditions.

Biomimetic cycloaddition approach to tropolone natural products via a tropolone ortho-quinone methide.

[reaction: see text] A study toward a possible biomimetic hetero Diels-Alder reaction is reported between humulene and a novel tropolone ortho-quinone methide. A suitable tropolone ortho-quinone methide precursor has been prepared from 3-methyl-2-furoate. Heating the ortho-quinone methide precursor gave a tropolone ortho-quinone methide, which in the presence of humulene underwent a hetero Diels-Alder reaction to give a deoxy analogue of epolone B.

Total synthesis of pyridovericin: studies toward the biomimetic synthesis of pyridomacrolidin.

[reaction: see text] The total synthesis of the novel metabolite pyridovericin 1 is reported. The synthesis of this key intermediate in our proposed biomimetic synthesis of pyridomacrolidin 2 has been accomplished in good yield from readily available 2,4-dihydroxypyridine.