A comparison of the benzylic and the allylic group as a donor in the formal [4+2] cycloaddition to tetrahydropyrans using donor-acceptor cyclobutanes

The allyl group was shown to be preferred over the benzyl group as a donor in the formal [4+2]-cycloaddition reaction between a donor-acceptor cyclobutane and various aldehydes to give tetrahydropyrans

A biosynthetically inspired route to substituted furans using the Appel reaction: total synthesis of the furan fatty acid F₅

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. Furthermore, this procedure has been used to deliver an effective total synthesis of the furan fatty acid (FFA) F5

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

A mild Lewis acid mediated epoxy-ester to bicyclic ortho ester rearrangemen

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 10 acid conditions

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. This transformation exhibited moderate to good substrate scope and has been shown to proceed by a 2-oxonia Cope rearrangement

Pyridone functionalization: regioselective deprotonation of 6-methylpyridin-2(1H)- and -4(1H)-one derivatives

Selective functionalization at the α-methyl group of 1-substituted pyridin-2(1H)- and 4(1H)-ones (2- and 4-pyridones) can be achieved by appropriate choice of base. n-Butyllithium was found to effect clean 6(2)-methyl deprotonation of 1-benzyl-2- and -4-pyridone derivatives, while potassium hexamethyldisilazide (KHMDS) was the preferred reagent for methyl deprotonation of the corresponding 1-methyl-2- and -4-pyridones. Deprotonation proceeds smoothly at –78 °C, and the resulting anions react readily with a wide range of electrophiles (aldehydes, ketones, alkylating reagents, and an azo compound) under precise temperature control to form usefully functionalized 2- and 4-pyridones and quinolizinones

Resolvin E1 (RvE1) 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 specialised pro-resolving lipid mediators (SPM’s) derived from dietary omega-3 fatty acids. Resolvin E1 (RvE1) 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, RvE1 attenuated mRNA gene expression levels of both interlukin-6 and monocyte chemoattractant protein-1 whilst having no effect on tumour necrosis factor-α or Interlukin-1β in C2C12 skeletal muscle myotubes. Findings at the molecular level were transferred into similar changes in extracellular protein levels of the corresponding genes with the greatest attenuation being noted in IL-6 protein concentrations. RvE1 instigated beneficial morphological changes through the prevention of endotoxin induced skeletal muscle atrophy, thus resulting in a rescue of endotoxin force losses in tissue engineered skeletal muscle. These findings demonstrate, in our model of endotoxin induced inflammation in skeletal muscle, that RvE1 has pro-resolving properties in this cell type. Our data provides rationale for further investigation into the mechanistic action of RvE1 in skeletal muscle, with the vision of having potential benefits for the prevention/resolution of in vivo skeletal muscle atrophy

Isolation and structure determination of the first example of the azeto[2,3-c]quinolizinedione ring system

An unexpected azeto[2,3-c]quinolizinedione has been isolated during synthetic studies on the base catalyzed condensation of ethyl 6-methylpyridin-2(1H)-on-1-ylacetate with benzil. Closure of a fused four-membered azetidinone ring occurred when potassium hexamethyldisilazide was employed as the base. The structure of the product was confirmed by synchrotron X-ray crystallography. A possible mechanism for the formation of the product is considered

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 C3-methyl group, and a Au(I)-catalyzed intermolecular hydroarylation to introduce the unsaturated ester

A general convergent strategy for the synthesis of tetra-substituted furan fatty acids (FuFAs)

Using a palladium catalyzed - acid mediated isomerization sequence, tetrasubstituted furans suitable for furan fatty acid (FuFA) total synthesis can be effectively constructed in high yield. This convergent approach installs the essential carbon side chains at the α1- and α2 -positions, the β1-methyl group, and importantly, an electron withdrawing group at the β2-position tempering the reactivity of the electron rich furan in the FuFAs. When this EWG is an ester, it was conveniently transformed into the required β1-methyl group in three high yielding synthetic steps. Using this approach, the total synthesis of 11D5 and 11D3 was accomplished in 7-steps from commercially available starting materials in overall yields of 52 % and 48 %, respectively. Furthermore, this methodology also provided an efficient synthetic route to the decarboxy analogues of both 11D5 and 11D3