Search

An approach to the α,β-unsaturated acyl azolium has been developed that exploits N-heterocyclic carbenes (NHCs) and acyl fluorides, without additional oxidants, bases, or preactivated pro-nucleophi...

While the enantioselective Rauhut-Currier reaction is established with bis(enone) substrates, it is yet to be reported with less electrophilic bis(enoate) substrates. By exploiting high-nucleophilicity N-heterocyclic carbenes, it is possible to achieve Rauhut-Currier reactions with these substrates. The reaction is demonstrated with a range of intramolecular reactions (20 examples) and six esterification/RC reaction cascades, which all proceed with high enantioselectivity (most >93:7 er).

The spiroketal moiety is an important privileged scaffold that occurs extensively in natural products, drugs, and bioactive molecules. Naturally occurring spiroketals are numerous, however aryl-fused spiroketals are relatively rare. The only comprehensive review disclosing the isolation, biological activity, and synthesis of benzannulated spiroketal natural products was published nearly a decade ago. This review will serve as an update of the 2009 review and include all known families of benzannulated spiroketals, detailing their isolation and biological activity where relevant. Although not exhaustive, endeavours towards their total synthesis will be discussed.

Amphibians have been declining around the world for more than four decades. One recognized driver of these declines is the chytrid fungus Batrachochytrium dendrobatidis, which causes the disease chytridiomycosis. Amphibians have complex and varied immune defenses against B. dendrobatidis, but the fungus also has a number of counterdefenses. Previously, we identified two small molecules produced by the fungus that inhibit frog lymphocyte proliferation, methylthioadenosine (MTA) and kynurenine (KYN). Here, we report on the isolation and identification of the polyamine spermidine (SPD) as another significant immunomodulatory molecule produced by B. dendrobatidis. SPD and its precursor, putrescine (PUT), are the major polyamines detected, and SPD is required for growth. The major pathway of biosynthesis is from ornithine through putrescine to spermidine. An alternative pathway from arginine to agmatine to putrescine appears to be absent. SPD is inhibitory at concentrations of ≥10 μM and is found at concentrations between 1 and 10 μM in active fungal supernatants. Although PUT is detected in the fungal supernatants, it is not inhibitory to lymphocytes even at concentrations as high as 100 μM. Two other related polyamines, norspermidine (NSP) and spermine (SPM), also inhibit amphibian lymphocyte proliferation, but a third polyamine, cadaverine (CAD), does not. A suboptimal (noninhibitory) concentration of MTA (10 μM), a by-product of spermidine synthesis, enhances the inhibition of SPD at 1 and 10 μM. We interpret these results to suggest that B. dendrobatidis produces an “armamentarium” of small molecules that, alone or in concert, may help it to evade clearance by the amphibian immune system.

Donor-acceptor cyclopropanes are known to serve as dipole precursors capable of engaging in (3+2) annulations with electron-deficient π-systems. In 2013, the reaction of donor-acceptor cyclopropanes with α,β-unsaturated acyl fluorides in an all-carbon (3+2) annulation was discovered. The reaction proceeds in good yields using the IMes NHC to provide diastereomerically pure β-lactone-fused cyclopentanes bearing four contiguous stereocentres. Subsequent studies demonstrated that N-t-butyl substituted homochiral morpholinone NHCs allowed the reaction to be achieved in up to 98 % ee. In this account, a background to this reaction is introduced, along with a complete account of the strengths, limitations and challenges encountered while developing this chemistry.

We have systematically studied the equilibrium structure and dynamics of a polymeric bicontinuous microemulsion (BμE) composed of poly(cyclohexylethylene) (PCHE), poly(ethylene) (PE), and a volumetrically symmetric PCHE-PE diblock copolymer, using dynamic mechanical spectroscopy, small angle X-ray and neutron scattering, and transmission electron microscopy. The BμE was investigated over an 80 °C temperature range, revealing a structural evolution and a rheological response not previously recognized in such systems. As the temperature is reduced below the point associated with the lamellar-disorder transition at compositions adjacent to the microemulsion channel, the interfacial area per chain of the BμE approaches that of the neat (undiluted) lamellar diblock copolymer. With increasing temperature, the diblock-rich interface swells through homopolymer infiltration. Time-temperature-superposed linear dynamic data obtained as a function of frequency show that the viscoelastic response of the BμE is strikingly similar to that of the fluctuating pure diblock copolymer in the disordered state, which we associate with membrane undulations and the breaking and reforming of interfaces. This work provides new insights into the structure and dynamics that characterize thermodynamically stable BμEs in the limits of relatively weak and strong segregation.

A series of 2-(3'-indolyl)tetrahydrofurans have been prepared by a DDQ-mediated oxidative cycloetherification process. Performing the reaction under biphasic conditions prevents reductive cleavage of the products by the spent oxidant (DDQH2).

Herein we report the enantioselective N-heterocyclic carbene catalyzed (4+2) annulation of the dienyl acyl azolium with enolates. The reaction exploits readily accessible acyl fluorides and TMS enol ethers to give a range of highly enantio- and diastereo-enriched cyclohexenes (most >97:3 er and >20:1 dr). The reaction was found to require high nucleophilicity NHC catalysts with mechanistic studies supporting a stepwise 1,6-addition/β-lactonization.

Donor-acceptor cyclopropanes are known to serve as dipole precursors capable of engaging in (3+2) annulations with electron-deficient π-systems. In 2013, the reaction of donor-acceptor cyclopropanes with α,β-unsaturated acyl fluorides in an all-carbon (3+2) annulation was discovered. The reaction proceeds in good yields using the IMes NHC to provide diastereomerically pure β-lactone-fused cyclopentanes bearing four contiguous stereocentres. Subsequent studies demonstrated that N-t-butyl substituted homochiral morpholinone NHCs allowed the reaction to be achieved in up to 98 % ee. In this account, a background to this reaction is introduced, along with a complete account of the strengths, limitations and challenges encountered while developing this chemistry.

A series of 2-(3′-indolyl)tetrahydrofurans have been prepared by a DDQ-mediated oxidative cycloetherification process. Performing the reaction under biphasic conditions prevents reductive cleavage of the products by the spent oxidant (DDQH2).

Methicillin-resistant Staphylococcus aureus pyruvate kinase (MRSA PK) has recently been identified as a target for development of novel antibacterial agents. Testing a series of 1,2-bis(3-indolyl)ethanes against MRSA PK has led to the discovery of a potent inhibitor that is selective over human isoforms.

The alpha 2 adrenergic agonist [3H]mivazerol labelled two populations of binding sites in membranes from the human striatum. Forty per cent of the sites labelled by 3 nM [3H]mivazerol corresponded to alpha 2 adrenergic receptors as they displayed a high affinity for (-)-adrenaline and for rauwolscine. The remaining binding was displaced by mivazerol with a pIC50 of 6.5 +/- 0.1. These sites displayed higher affinity for dexmedetomidine (pIC50 = 7.1 +/- 0.1), but much lower affinity for clonidine (pIC50 < 5.0) and for idazoxan (pIC50 = 5.1 +/- 0.1). Mivazerol also showed low affinity for the [3H]clonidine-labelled I1 imidazoline receptors and for the [3H]idazoxan-labelled I2 receptors (pIC50 = 5.1 and 3.9, respectively). These results suggest that the non-adrenergic [3H]mivazerol binding sites are distinct from the imidazoline receptors in the human striatum.

Chinook salmon smolt in fresh water fed a commercial diet known to produce minimal gastric dilation and air sacculitis (GDAS) were randomly assigned to four experimental tanks with flow-through sea water. All four groups were acclimatized to sea water for 3 weeks and fed a diet of minced fresh seafood. After 3 weeks the groups were fed either; seafood as before, a different commercial pelleted diet associated with the development of GDAS on farms, or either diet supplemented with 500 mg L - 1 putrescine, 300 mg L - 1 cadaverine and 250 mg L - 1 tyramine. Gastric dilation was produced in fish fed the commercial diet for 1 month but not by feeding a diet of minced seafood. The addition of putrescine, cadaverine and tyramine to either diet had no significant effect on the development of gastric dilation. Fish fed the commercial diet had significantly (P < 0.0001) wider weight-adjusted stomach widths, less prominent longitudinal stomach folds (P < 0.0001) and lower (P < 0.0001) stomach-width ratios than fish fed the fresh seafood diet. There was no significant difference in serum osmolality or sodium concentration between fish from groups with or without gastric dilation or fed biogenic amines.

Cycloaddition reactions of substituted α,β-unsaturated esters with various electronich olefins lead to 6-alkoxy-3,4-dihydro-2H-pyrans.

not available

Summary The effect of three anaesihetic techniques on blood loss and intra-uterine pressure changes in response io Syntocinon were siudied in patients undergoing routine first trimester suciion termination of pregnancy. All patients received a standard premedicaiion, a bolus dose of fentanyl, intravenous induction of anaesthesia and maintenance with nitrous oxide and oxygen plus either iniravenous supplementation or 0.5% halothane. Intra-uterine pressure was related to ihe anaesthetic technique used although blood loss was unrelaied either to anaesthetic technique or to intra-uterine pressure changes.

The rates of oxidation of lumiflavin radical by ferricyanide, indole radical and oxygen are decreased by factors of four to ten as a result of complexation with tryptophan. Tyrosine, methionine and glycine were found not to measurably alter the flavin radical reactivity. Similar results were obtained using flavinyl peptides in which tryptophan or methionine were covalently linked to the flavin. These observations suggest that one of the consequences of the interaction between the flavin and a tryptophan side chain in the coenzyme binding site of the flavodoxins is to deactivate the semiquinone form of the enzyme towards oxidizing agents, thereby increasing its stability.