Lipopolysaccharide (LPS) is the main inducer of shock and death in Gram-negative sepsis. Recent evidence suggests that LPS-induced signal transduction begins with CD14-mediated activation 1 or more Toll-like receptors (TLRs). The lipid A analogues IVa Rhodobacter sphaeroides (RSLA) exhibit an uncommon species-specific pharmacology. Both compounds inhibit effects LPS human cells but display LPS-mimetic activity hamster cells. We transfected TLR4 TLR2 into fibroblasts to determine if either...

Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS). MD-2 is associated with TLR4 and imparts LPS responsiveness to it. Little known, however, as whether directly regulates recognition by TLR4. To address the issue, we took advantage of a species-specific pharmacology lipid IVa, an analogue A. Lipid IVa acted agonistically on mouse (m) TLR4/MD-2 but not human (h) TLR4/MD-2. antagonized agonistic effect A hTLR4/MD-2. We examined chimeric complex consisting mTLR4 hMD-2 ask species...

Lipopolysaccharides (LPS, endotoxin) represent a major virulence factor of Gram‐negative bacteria, which can cause septic shock in mammals, including man. The lipid anchor LPS to the bacterial outer membrane, A, exhibits peculiar chemical structure, harbours ‘endotoxic principle’ and is also responsible for expression pathophysiological effects. Chemically modified A be endotoxically inactive, but may express strong antagonistic activity against active LPS. By applying orientation...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal Synthesis of (-)-Grayanotoxin IIIToshiyuki Kan, Seijiro Hosokawa, Shinji Nara, Masato Oikawa, Shinya Ito, Fuyuhiko Matsuda, and Haruhisa ShirahamaCite this: J. Org. Chem. 1994, 59, 19, 5532–5534Publication Date (Print):September 1, 1994Publication History Published online1 May 2002Published inissue 1 September 1994https://pubs.acs.org/doi/10.1021/jo00098a009https://doi.org/10.1021/jo00098a009research-articleACS PublicationsRequest reuse...

Three sequential efficient glycosylation reactions starting from D-glucosamine were used in the first total synthesis of Escherichia coli Re lipopolysaccharide, which is one most simple lipopolysaccharides found on surface living bacteria.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal Synthesis of TautomycinMasato Oikawa, Tohru Ueno, Hideaki and Akitami IchiharaCite this: J. Org. Chem. 1995, 60, 16, 5048–5068Publication Date (Print):August 1, 1995Publication History Published online1 May 2002Published inissue 1 August 1995https://pubs.acs.org/doi/10.1021/jo00121a026https://doi.org/10.1021/jo00121a026research-articleACS PublicationsRequest reuse permissionsArticle Views2347Altmetric-Citations90LEARN ABOUT THESE...

Abstract We report herein an efficient synthesis of fully Boc‐protected, up to 13‐meric polymer 1,3‐propanediamine. The was facilitated by one‐pot conversion (up six) N ‐Ns groups ‐Boc under conditions 1) PhSH and Cs 2 CO 3 for deprotection the Ns group, followed 2) Boc O protection. average yield per group extremely high, especially substrates with four six (94.6%–96.6%).

A synthesis of the C14-C35 segment macrolide ring model poecillastrin C has been achieved. The C14-C23 was synthesized by stereoselective Mukaiyama aldol reaction between ketene silyl N,O-acetal possessing chiral oxazolidinone auxiliary and O-acetyl lactol prepared conjugate addition followed iodolactonization. C24-C35 constructed three vinylogous reactions. Both segments were coupled diisobutylaluminium hydride (DIBALH) reduction to produce moiety macrocyclic model.

Abstract A convergent, iterative, and split-couple strategy for synthesis of homogeneous polymer 1,3-propanediamine (long-chain polyamine, LCPA) has been developed, by employing 1,3-dibromopropane as a glue in subunit couplings. By this synthetic strategy, 7-, 11-, 15-mer LCPAs were successfully synthesized. This solved problems that had arisen with previous methods, such variable reactivity poor reproducibility.

Here described is the reduction of 4,6-O-benzylidene functionalities D-glucose or D-glucosamine with various protecting groups by borane dimethylamine complex and boron trifluoride etherate. The 4-O-benzyl products were selectively obtained when reaction was carried out in dichloromethane for substrates 3-O-benzyl groups. In contrast, acetonitrile provided 6-O-benzyl predominantly 3-O-protected other forms than a benzyl ether.

The chemical structure of a novel lipid A, which was obtained as major component from lipopolysaccharide Helicobacter pylori strain 206-1, determined to be glucosamine β(1-6) disaccharide 1-(2-aminoethyl)phosphate acylated by (R)-3-hydroxyoctadecanoic acid and (R)-3-(octadecanoyloxy)octadecanoic at the 2- 2′-position, respectively. absence phosphoryl group 4′-position fatty acyl groups 3- 3′-position, stoichiometric presence 2-aminoethyl phosphate 1-position are unique features,...

LIM-kinases (LIMKs) play crucial roles in various cell activities, including migration, division, and morphogenesis, by phosphorylating inactivating cofilin. Using a bimolecular fluorescence complementation assay to detect the actin-cofilin interaction, we screened LIMK1 inhibitors identified two effective inhibitors, damnacanthal (Dam) MO-26 (a pyrazolopyrimidine derivative). These compounds have already been shown inhibit Lck, Src family tyrosine kinase. However, vitro kinase assays...

A synthetic lipid of Helicobacter pylori strain 206-1 (compound HP206-1), which is similar to its natural A, exhibited no or very low endotoxic activities as compared Escherichia coli-type 506). Furthermore, compound HP206-1 well demonstrated mitogenic responses in murine spleen cell. On the other hand, showed a weaker but significant production interleukin-8 gastric cancer cell line, MKN-1, comparison with 506. induction tumor necrosis factor-α human peripheral blood mononuclear cells and...

We demonstrate a highly sensitive imaging method combined terahertz time-domain spectroscopy and an interference effect for label-free protein detection on polyvinylidene difluoride membrane. The is based uses effect. Biotin linked to the membrane using poly ethylene glycol or methyl ether prevent it from being washed off. Binding of biotin with streptavidin then observed by measuring signal change due variation refractive index. binding in gradually decreasing concentrations, down 27 ng...

Abstract A highly regioselective domino metathesis reaction of 7‐oxanorbornene was developed that employed an intramolecular association amide carbonyl group to a ruthenium metal centre. By using this reaction, twelve glutamate analogues inspired by dysiherbaine were efficiently synthesized over 12–14 steps; one the exhibited bioactivity consistent with central nervous system depression.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Here, we report an unprecedented, highly diastereoselective Prins-Ritter reaction of aldehydes, homoallylic alcohols, and nitriles in a three-component coupling for the synthesis tetra-cis-substituted 4-amidotetrahydropyrans. In this study, was not only applied carbohydrate-based heterobicycles but also more complex heterotricycles, showing acceptable levels conversion yield (42-97% BRSM) exclusive diastereoselectivity. Furthermore, latter heterotricycles were converted to nine analogues our...

Abstract Lipid A and its two chemically stable analogues, wherein the glycosidic phosphoryl groups in lipid is replaced with 2-(phosphonooxy)ethyl or carboxymethyl groups, have been synthesized by an improved divergent route via a common allyl glycoside intermediate which 4-hydroxy group was protected as benzyl ether. The total yields were more than 20% for 11 12 steps starting from 4,6-O-benzylidene-2-deoxy-2-(trichloroethoxycarbonylamino)-d-glucopyranoside. These synthetic analogues induce...

Dysiherbaine (1) and its congener neodysiherbaine A (2) are naturally occurring excitatory amino acids with selective potent agonistic activity for ionotropic glutamate receptors. We describe herein the total synthesis of 2 structural analogues 3−8. Advanced key intermediate 16 was employed as a branching point to assemble series these 3−8 respect C8 C9 functionalities, which would not have been accessible through manipulations natural product itself. The features (i) stereocontrolled...

The complete absolute configuration of goniodomin A, an actin-targeting polyether macrolide isolated from the marine dinoflagellate Alexandrium hiranoi, was established analysis ROESY experiments and coupling constants, synthesis suitable model compounds for NMR spectroscopic comparisons, degradation experiments, correlation with synthetic reference compounds.

In this article a regioselective domino metathesis reaction of unsymmetrical 7-oxanorbornenes, readily available by tandem Ugi/Diels-Alder as key step, promoted the Hoveyda-Grubbs second-generation catalyst in presence electron-rich vinyl acetate cross (CM) substrate is reported. The mechanism for unusually high regioselectivity observed CM was investigated, and course where Fischer-type carbene ["Ru"= CH(OAc)] generates steric interaction proposed. products were further converted to four...

Investigations are reported into the interaction of lipid A, 'endotoxic principle' bacterial lipopolysaccharide (LPS), with phospholipid membranes in absence and presence an acute-phase transport protein, lipopolysaccharide-binding protein (LBP) applying Fourier-transform infrared (FTIR) fluorescence resonance energy transfer (FRET) spectroscopy. In LBP, intermixing phospholipids A takes place on time-scale hours, while LBP this process order minutes. comparison chemically different shows...

Our early work using homogeneous synthetic preparations demonstrated the presence of a lipid A analog which antagonizes endotoxic activities LPS and A. The first example was tetraacylated biosynthetic precursor, now known as precursor Ia or IVa, that contains four 3-hydroxytetradecanoyl moieties linked to bisphosphorylated disaccharide backbone common hexa-acyl Escherichia coli Various compounds with both antagonistic have subsequently been reported from either natural sources, but little is...