Aryl-Allene Cyclization via a Hg(OTf)2-Catalytic Pathway.

Hg(OTf)2-catalyzed aryl-allene cyclization accompanied by formation of a quaternary carbon center has been realized. Deuterium-labeling experiments and computational modeling were used to propose a novel catalytic pathway involving direct H-transfer from the aromatic ring to the vinyl mercury moiety followed by mercury 1,2-migration.

Vizantin inhibits endotoxin-mediated immune responses via the TLR 4/MD-2 complex.

Vizantin has immunostimulating properties and anticancer activity. In this study, we investigated the molecular mechanism of immune activation by vizantin. THP-1 cells treated with small interfering RNA for TLR-4 abolished vizantin-induced macrophage activation processes such as chemokine release.

Concise synthesis of a probe molecule enabling analysis and imaging of vizantin.

Trehalose 6,6'-dicorynomycolate (TDCM) was first characterized in 1963 as a cell surface glycolipid of Corynebacterium spp. by Ioneda and co-workers. TDCM shows potent anti-tumor activity due to its immunoadjuvant properties.

Novel inhibitor of bacterial sphingomyelinase, SMY-540, developed based on three-dimensional structure analysis.

Context: Bacterial sphingomyelinase (SMase) is thought to play a crucial role in bacterial evasion of the immune response during the early stages of infections.

Objective: The objective of this study was to predict the chemical structure required for competitive SMase inhibition, then synthesize and test the effect of potential inhibitors on the hydrolysis of sphingomyelin (SM) and protection against infection by Bacillus cereus.

Materials And Methods: We synthesized 10 potential SMase inhibitors, derivatives of RY221B-a analogues, based on predictions from three-dimensional structural analysis.

Development of vizantin, a safe immunostimulant, based on the structure-activity relationship of trehalose-6,6'-dicorynomycolate.

Vizantin, 6,6'-bis-O-(3-nonyldodecanoyl)-α,α'-trehalose, was developed as a safe immunostimulator on the basis of a structure-activity relationship (SAR) study with trehalose 6,6'-dicorynomycolate (TDCM). It was possible to synthesize vizantin on a large scale more easily than in the case of TDCM, and the compound exhibited more potent prophylactic effect on experimental lung metastasis of B16-F0 melanoma cells. Because vizantin stimulated human macrophages, it is a promising candidate for clinical application.

Hg(OTf)2-catalyzed vinylogous semi-pinacol rearrangement leading to 1,4-dihydroquinolines.

An efficient method for the construction of dihydroquinoline derivatives possessing a quaternary carbon center is developed by an application of Hg(OTf)(2)-catalyzed vinylogous semi-pinacol-type rearrangement. The reaction was found to be specifically catalyzed by mercury salt and to proceed via a bicyclic aminal.

Syntheses of structurally-simplified and fluorescently-labeled neovibsanin derivatives and analysis of their neurite outgrowth activity in PC12 cells.

The syntheses of several neovibsanin derivatives were carried out in order to elucidate the simple structure required for displaying neurite outgrowth activity. In addition, a fluorescent probe molecule was synthesized and the analysis of its behavior in the PC12 cell line showed that the neovibsanins accumulate on the outer edge of the cell at the site of formation of prominences.

Synthesis and evaluation of novel phosphate ester analogs as neutral sphingomyelinase inhibitors.

A novel sphingomyelin inhibitor RY221B-a, which contains a bipyridyl moiety as a metal coordination site was designed based upon the mechanism of phosphate ester hydrolysis. RY221B-a was synthesized from N-Boc-sphingosine in three steps via selective etherification using stannyl acetal. Synthesized RY221B-a exhibited relatively-strong inhibitory activity against Bc-SMase (IC(50)=1.

A new catalyst for organic synthesis: mercuric triflate.

Herein, we describe Hg(OTf)(2) as a new catalytic system for organic synthesis, which can achieve the hydration of alkynes, C-C bond forming cyclizations, heterocycle synthesis and cyclization initiated by allylic alcohols at very high catalytic turnovers under mild conditions. The first solid-supported mercuric salt, silaphenylmercuric triflate, was also developed and found to act as a powerful catalyst for most Hg(OTf)(2)-catalyzed reactions.

4-Aminopyridine catalyzed direct and regioselective acylation of N-tosylhydrazide.

An efficient and simple method for selective acylation of either one of two nitrogen atoms of tosylhydrazide was developed. The selectivity was drastically controlled by a catalytic amount of 4-aminopyridine or 4-(dimethylamino)pyridine with common acylating agents. The nitrogen atom masked with a tosyl group was acylated in the presence of 4-aminopyridine, whereas the primary nitrogen atom was acylated in the absence of 4-aminopyridine.

Total synthesis of (+/-)-neovibsanin B.

(+/-)-Neovibsanin B was synthesized based on a DMI-accelerated intramolecular Diels-Alder reaction followed by oxy-Michael addition-lactonization. The synthetic (+/-)-neovibsanin B induced similar morphological changes in NGF-mediated PC12 cells compared with natural (+)-neovibsanin B.

Silaphenylmercuric triflate catalyzed reactions: synthesis of a solid-supported mercuric salt catalyst.

Let it flow, let it flow: A procedure to generate the first solid-supported mercuric salt, silaphenylmercuric triflate, is described. Silaphenylmercuric triflate showed remarkable catalytic activity for an indole synthesis, furanoyne cyclization, arylyne cyclization, and tandem carbocyclizations. An efficient flow reaction system for indole synthesis and arylyne cyclization is also described (see figure).

Ascochytatin, a novel bioactive spirodioxynaphthalene metabolite produced by the marine-derived fungus, Ascochyta sp. NGB4.

Ascochytatin, a new spirodioxynaphthalene metabolite produced by a marine-derived fungus, was found from a screening program focused on the bacterial two-component regulatory system. The structure of ascochytatin was determined by spectroscopic methods, including NMR and MS. The relative stereochemistry was determined by an X-ray crystallographic analysis, and the absolute stereochemistry was determined by the modified Mosher's method.

Structural basis of actin recognition and arginine ADP-ribosylation by Clostridium perfringens iota-toxin.

The ADP-ribosylating toxins (ADPRTs) produced by pathogenic bacteria modify intracellular protein and affect eukaryotic cell function. Actin-specific ADPRTs (including Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin) ADP-ribosylate G-actin at Arg-177, leading to disorganization of the cytoskeleton and cell death. Although the structures of many actin-specific ADPRTs are available, the mechanisms underlying actin recognition and selective ADP-ribosylation of Arg-177 remain unknown.

Hg(OTf)2-catalyzed arylene cyclization.

Novel Hg(OTf) 2-catalyzed arylene cyclization was achieved with highly efficient catalytic turnover (up to 200 times). The reaction takes place via protonation of allylic hydroxyl group by in situ formed TfOH of an organomercuric intermediate to generate a cationic species. Subsequent smooth demercuration regenerates the catalyst.

The relationship between the metabolism of sphingomyelin species and the hemolysis of sheep erythrocytes induced by Clostridium perfringens alpha-toxin.

Clostridium perfringens alpha-toxin induces the hemolysis of sheep erythrocytes by activating the metabolism of sphingomyelin (SM) via a GTP binding protein in membranes. alpha-Toxin stimulated the formation of 15-N-nervonoyl sphingosine (C24:1-ceramide), which was identified by positive ion fast atom bombardment-MS and 1H-NMR spectroscopy. C24:1-ceramide stimulated the toxin-induced hemolysis of saponin-pretreated sheep erythrocytes and increased the production of sphingosine 1-phosphate (S1P) in the cells, but N-lignoceroyl sphingosine did not.

Virtually complete E-selective alpha,beta-unsaturated ester synthesis by Hg(OTf)2-catalyzed hydration of sec-ethoxyalkynyl acetate.

The reaction of alkyl-substituted sec-ethoxyalkynyl acetates with water catalyzed by Hg(OTf)2 afforded alpha,beta-unsaturated esters in excellent yield with high catalytic turnover up to 1000 times under very mild reaction conditions with virtually complete E-selectivity, superior even to that of the HWE reaction.

Effect of unsaturated bonds in the sn-2 acyl chain of phosphatidylcholine on the membrane-damaging action of Clostridium perfringens alpha-toxin toward liposomes.

Clostridium perfringens alpha-toxin degrades phosphatidylcholine (PC) in the bilayer of liposomes and destroys the membrane. The effect of the type and position of unsaturation in the fatty acyl chain of PC (18:0/18:1 PC) synthesized on the toxin-induced leakage of carboxyfluorescein (CF) from PC liposomes was examined. Differential scanning calorimetry showed that the phase transition temperature (T(m)) was minimal when the triple bond was positioned at C (9) in the sn-2 acyl chain.

Catalytic activation of the leaving group in the S(N)2 reaction.

A novel catalytic activation of the leaving group in the S(N)2 reaction is achieved as an extension of our mercuric triflate-catalyzed reactions. Derivatives of anilinoethyl 4-pentynoate reacted smoothly with catalytic amounts of Hg(OTf)(2) to give indoline derivatives in excellent yield with efficient catalytic turnovers under very mild conditions. The reaction of optically pure secondary alcohol derivatives resulted in inversion of stereochemistry, which is a definitive feature of the S(N)2 reaction.

Urukthapelstatin A, a novel cytotoxic substance from marine-derived Mechercharimyces asporophorigenens YM11-542. II. Physico-chemical properties and structural elucidation.

The new cyclic peptide antibiotic, urukthapelstatin A, has been isolated from a culture of Thermoactinomycetaceae bacterium Mechercharimyces asporophorigenens YM11-542. The structure of urukthapelstatin A was elucidated by NMR, MS, Marfey analysis, chiral HPLC and X-ray crystal analyses.

Hg(OAc)(2).0.1Sc(OTf)(3)-catalyzed cycloisomerization of 2-(4-pentynyl)furan.

[structure: see text]. Although the Hg(OTf)2.3TMU-catalyzed Friedel-Crafts-type reaction of 3-(4-pentynyl)furan afforded the exo cyclization product, the reaction of 2-(4-pentynyl)furan furnished a very low yield.

Efficient syntheses of a series of trehalose dimycolate (TDM)/trehalose dicorynomycolate (TDCM) analogues and their interleukin-6 level enhancement activity in mice sera.

We found an IL-6 level-enhancing compound during our synthetic study of trehalose-6,6'-dimycolate (1, TDM, formerly called cord factor) analogues. TDM is a glycolipid distributed in the cell wall of Mycobacterium tuberculosis and shows significant antitumor activity based on an immunoadjuvant activity. However, due to its significant toxicity, TDM is not yet applicable for practical use.