Eicosanoids are critical mediators of fever, pain, and inflammation generated by immune and tissue cells. We recently described a new bioactive eicosanoid generated by cyclooxygenase-1 (COX-1) turnover during platelet activation that can stimulate human neutrophil integrin expression. On the basis of mass spectrometry (MS/MS and MS), stable isotope labeling, and GC-MS analysis, we previously proposed a structure of 8-hydroxy-9,11-dioxolane eicosatetraenoic acid (DXA).
View Article and Find Full Text PDFRe-investigation of the l-proline catalyzed double aldol cascade dimerization of succinaldehyde for the synthesis of a key bicyclic enal intermediate, pertinent in the field of stereoselective prostaglandin synthesis, is reported. The yield of this process has been more than doubled, from 14 % to a 29 % isolated yield on a multi-gram scale (32 % NMR yield), through conducting a detailed study of the reaction solvent, temperature, and concentration, as well as a catalyst screen. The synthetic utility of this enal intermediate has been further demonstrated through the total synthesis of Δ -prostaglandin J , a compound with known anti-leukemic properties.
View Article and Find Full Text PDFA hydrogen-transfer strategy for the catalytic functionalization of benzylic alcohols via electronic arene activation, accessing a diverse range of bespoke diaryl ethers and aryl amines in excellent isolated yields (38 examples, 70% average yield), is reported. Taking advantage of the hydrogen-transfer approach, the oxidation level of the functionalized products can be selected by judicious choice of simple and inexpensive additives.
View Article and Find Full Text PDFN-Acetylneuraminate lyase is the first committed enzyme in the degradation of sialic acid by bacterial pathogens. In this study, we analyzed the kinetic parameters of N-acetylneuraminate lyase from methicillin-resistant Staphylococcus aureus (MRSA). We determined that the enzyme has a relatively high K of 3.
View Article and Find Full Text PDFGlycosylation of a fully armed donor bearing a 2-O-(trimethoxybenzenethiol) ethyl ether protecting group is completely α-selective with a range of carbohydrate alcohol acceptors. Low-temperature NMR studies confirm the intermediacy of cyclic sulfonium ion intermediates arising from six-membered β-sulfonium ring neighboring group participation. Selective protecting group removal is achieved in high yield in a single operation by S-methylation and base-induced β-elimination.
View Article and Find Full Text PDFA series of arabinose glycosyl sulfamides with varying alkyl chain types and lengths were synthesised as mimics of decaprenolphosphoarabinose (DPA), and as potential inhibitors of mycobacterial cell wall biosynthesis. Unprecedented conversion of the desired furanose to the thermodynamically more stable pyranose form occurred during final de-protection. Biological testing against Mycobacterium smegmatis revealed low to moderate anti-mycobacterial activity with marked dependence on alkyl chain length, which in the case of mono-substituted sulfamides was maximal for a C-10 chain.
View Article and Find Full Text PDFA flavinium catalyst, in conjunction with hydrogen peroxide as stoichiometric oxidant, allowed the aqueous conversion of non-protected thioglycosides into the corresponding glycosyl sulfoxides. These glycosyl sulfoxides displayed only very weak inhibitory activity against corresponding glycosidases.
View Article and Find Full Text PDFAntiviral resistance is currently monitored by a labelled enzymatic assay, which can give inconsistent results because of the short half-life of the labelled product, and variations in assay conditions. In this paper, we describe a competitive surface plasmon resonance (SPR) inhibition assay for measuring the sensitivities of wild-type neuraminidase (WT NA) and the H274Y (histidine 274 tyrosine) NA mutant to antiviral drugs. The two NA isoforms were expressed in High-five™ (Trichoplusia ni) insect cells.
View Article and Find Full Text PDFInfluenza is one of the most common infections of the upper respiratory tract. Antiviral drugs that are currently used to treat influenza, such as oseltamivir and zanamivir, are neuraminidase (NA) inhibitors. However, the virus may develop resistance through single-point mutations of NA.
View Article and Find Full Text PDFThe conversion of sugars into glycomimetics typically involves multiple protecting-group manipulations. The development of methodology allowing the direct aqueous conversion of free sugars into glycosides, and mimics of oligosaccharides and glycoconjugates in a high-yielding and stereoselective process is highly desirable. The combined use of 2-azido-1,3-dimethylimidazolinium hexafluorophosphate and the Cu-catalyzed Huisgen cycloaddition allowed the synthesis of a range of glycoconjugates in a one-step reaction directly from reducing sugars under aqueous conditions.
View Article and Find Full Text PDFActa Crystallogr Sect F Struct Biol Cryst Commun
March 2013
The enzyme N-acetylneuraminate lyase (EC 4.1.3.
View Article and Find Full Text PDFLipoylation, the covalent attachment of lipoic acid to 2-oxoacid dehydrogenase multi-enzyme complexes, is essential for metabolism in aerobic bacteria and eukarya. In Escherichia coli, lipoylation is catalysed by LplA (lipoate protein ligase) or by LipA (lipoic acid synthetase) and LipB [lipoyl(octanoyl) transferase] combined. Whereas bacterial and eukaryotic LplAs comprise a single two-domain protein, archaeal LplA function typically involves two proteins, LplA-N and LplA-C.
View Article and Find Full Text PDFRuthenium-catalysed hydrogen transfer has been successfully used for the conversion of alcohols into either 2,3-dihydroquinazolines or quinazolines. The choice of reaction conditions allows for the selective formation of either heterocycle and the methodology can also be applied to the sulfonamide analogue.
View Article and Find Full Text PDFApplication of microwave heating to the Borrowing Hydrogen strategy to form C-N bonds from alcohols and amines is presented, removing the need for solvent and reducing the reaction times while still yielding results comparable with those using thermal heating.
View Article and Find Full Text PDFRemote electronic activation of benzylic alcohols via temporary oxidation facilitates ruthenium-catalyzed arene C-H activation for a range of aromatic alcohols.
View Article and Find Full Text PDFThe synthesis of secondary amides from primary alcohols and amines has been developed using commercially available [Ru(p-cymene)Cl(2)](2) with bis(diphenylphosphino)butane (dppb) as the catalyst.
View Article and Find Full Text PDFThe alkylation of amines by alcohols has been achieved using 0.5 mol % [Ru(p-cymene)Cl(2)](2) with the bidentate phosphines dppf or DPEphos as the catalyst. Primary amines have been converted into secondary amines, and secondary amines into tertiary amines, including the syntheses of Piribedil, Tripelennamine, and Chlorpheniramine.
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