Strontium-mediated selective protonation of unsaturated linkage of aromatic hydrocarbons and these derivatives

The selective protonation of aromatic hydrocarbons with at least two or more aromatic rings and aromatic compounds bearing unsaturated linkages can be achieved by metallic strontium metal with ammonium chloride and iodine, or ammonium iodide in tetrahydrofuran. The reaction system is ammonia-free in room temperature and the reaction proceeds high selectivity in moderate to good yields

Formation and characterization of phosphatidylethanolamine/lysophosphatidylcholine mixed vesicles

AbstractThe lipid aggregates formed by adding lysophosphatidylcholine (lysoPC) solution to phosphatidylethanolamine (PE) dispersion at 4°C followed by incubating it at 37°C were proved to be a vesicle system judged from the negatively stained electron micrographs and the latency of calcein fluorescence. The results obtained are analogous to those described for phosphatidylcholine (PC) vesicles. The chromatography results showed that the incorporation of PE and lysoPC into the PE/lysoPC vesicles was in a molar ratio of 5 to 2. The PE/lysoPC membrane was found to have similar barrier potentials for Cl− or calcein efflux to the PC membrane. 1H Nuclear magnetic resonance measurement suggested that lysoPC dominated the external monolayer of the vesicles. Furthermore, it was found that PE/lysoPC vesicles and micelles could coexist when a large amount of lysoPC was added to the PE/lysoPC vesicle suspension. The formation of PE/lysoPC vesicles is discussed in combination with the inhibition of interlayer attachment by lysoPC from the PE membrane

Three-component, one-pot tandem Sonogashira/Suzuki–Miyaura coupling reactions and derivatization for the synthesis of a library of ceramide-transport protein inhibitors that were designed in silico

We have developed a one-pot, tandem Sonogashira/Suzuki–Miyaura coupling reaction, which is unknown synthetically, and applied it for the synthesis of a library of potential natural ligand nonmimetic inhibitors of the lipid-transfer protein, ceramide-transport protein (CERT). The characteristic feature of this reaction is that the two-step coupling reaction proceeds smoothly with only 5 mol% of palladium catalyst. Furthermore, the location of the formed carbon–carbon bond would be strictly defined because of the difference in reactivity. Therefore, many derivatives could be synthesized in high yields without the formation of regioisomeric byproducts by the same procedure. We also performed a semi-gram scale synthesis of several derivatives to provide the bioactive assey. After synthesizing as many as 113 derivatives, we identified a nonnatural mimetic inhibitor with activity comparable to that of the known inhibitor (1R,3S)-HPA-12

Methoxycarbonyl Group as a Conformational Regulator for The Benzene Ring of Triphenylamines

A series of triphenylamine derivatives bearing a methoxycarbonyl group on the benzene ring was synthesized. The structural and physical properties based on the introduction of the methoxycarbonyl group into benzene ring were investigated by single crystal X-ray diffraction, computational studies and spectroscopic methods. It was revealed that the methoxycarbonyl group has not only structural control but also a definite electronic effect on the triphenylamine structure

Chlamydial Infection-Dependent Synthesis of Sphingomyelin as a Novel Anti-Chlamydial Target of Ceramide Mimetic Compounds

The obligate intracellular bacterium Chlamydia trachomatis is the major causative agent of bacterial sexually transmitted diseases worldwide. In infected cells, the ceramide transport protein (CERT) is recruited to inclusions, where C. trachomatis replicates using host-synthesized ceramide. The ceramide is converted to sphingomyelin (SM) by a chlamydial infection-dependent SM synthesis (cidSM-synthesis) pathway, which occurs even in the absence of the SM synthases (SMS)-1 and -2 of host cells. The ceramide mimetic compound (1R,3S)-HPA-12 and the nonmimetic compound E16A, both of which are potent inhibitors of CERT, repressed the proliferation of C. trachomatis in HeLa cells. Unexpectedly, (1R,3R)-HPA-12, a ceramide mimetic compound that lacks CERT inhibitory activity, also exhibited potent anti-chlamydial activity. Using endogenous SMS-knockout mutant HeLa cells, we revealed that (1R,3R)-HPA-12 mildly inhibited cidSM-synthesis. In addition, LC-MS analysis revealed that (1R,3R)-HPA-12 is converted to a phosphocholine-conjugated metabolite in an infection-dependent manner. Imaging analysis with a fluorescent analog of ceramide suggested that cidSM-synthesis occurs in the bacterial bodies and/or inclusions. Collectively, these results suggested that (1R,3R)-HPA-12 exerts its anti-chlamydia activity not only as an inhibitor of cidSM-synthesis, but also via putative toxic effects of its phosphocholine adduct, which is most likely produced by the cidSM-synthesis route

Aerobic oxidation of alcohols using bismuth bromide as a catalyst

We developed an environmentally friendly method for aerobic oxidation of alcohols using a commercially available, relatively benign bismuth salt as a catalyst. We found that the catalytic combination of BiBr3 with nitric acid is key for enhancing the reactivity. The reaction proceeds well under air, making the use of pure oxygen unnecessary. Each of the primary or secondary alcohols tested was oxidized to the corresponding aldehydes or ketones using this protocol

Environmentally Benign Ritter Reaction Using Bismuth Salts as a Catalyst

We developed an environmentally benign Ritter reaction of alcohols with nitriles using a commercially available bismuth salt as a less harmful catalyst. The detailed reaction profiles revealed that consumption of the ether by-product as the reaction proceeded was the key for optimizing this reaction, and the yield of the target amide was improved by adding a small amount of water. This finding clearly reveals the significance of using a bismuth salt as the catalyst, as it is not deactivated in the presence of water. This catalyst system has a broad substrate scope, and even with 1 mol% of the catalyst, the reaction progresses smoothly. It is also possible to react stoichiometric amounts of nitriles and alcohols, thus reducing the amount of organic solvent required for the reaction. Furthermore, as the inexpensive bismuth catalyst can be easily removed using aqueous hydrochloric acid, a purification process that only required washing and drying without any organic solvents was successfully established

The pathophysiology of prospective memory failure after diffuse axonal injury - Lesion-symptom analysis using diffusion tensor imaging

<p>Abstract</p> <p>Background</p> <p>Prospective memory (PM) is one of the most important cognitive domains in everyday life. The neuronal basis of PM has been examined by a large number of neuroimaging and neuropsychological studies, and it has been suggested that several cerebral domains contribute to PM. For these activation studies, a constellation of experimental PM trials was developed and adopted to healthy subjects. In the present study, we used a widely used clinical PM assessment battery to determine the lesions attributable to PM failure, with the hypothesis that lesion-symptom analysis using diffusion tensor imaging (DTI) in subjects with diffuse axonal injury (DAI) can reveal the neuronal basis of PM in everyday life.</p> <p>Results</p> <p>Fourteen DAI patients (age: range of 18-36, median 24) participated in this study. PM failure was scored in the range of 0-6 using three sub-tests of the Rivermead Behavioural Memory Test. The PM scores of DAI patients were in the range of 2-6 (median 4.5, inter-quartile range 2.25). The severity of axonal injury following DAI was examined using fractional anisotropy (FA), one of the DTI parameters, at voxel level in each subject. We then obtained clusters correlated with PM failure by conducting voxel-based regression analysis between FA values and PM scores. Three clusters exhibited significant positive correlation with PM score, the left parahippocampal gyrus, left inferior parietal lobe, and left anterior cingulate.</p> <p>Conclusions</p> <p>This is the first lesion-symptom study to reveal the neuronal basis of PM using DTI on subjects with DAI. Our findings suggest that the neuronal basis of PM is in the left parahippocampal gyrus, left inferior parietal lobe, and/or left anterior cingulate. These findings are similar to those of previous activation studies with loading experimental PM tasks.</p

Direct conversion of carlactonoic acid to orobanchol by cytochrome P450 CYP722C in strigolactone biosynthesis

Strigolactones (SLs) are carotenoid-derived phytohormones and rhizosphere signaling molecules for arbuscular mycorrhizal fungi and root parasitic weeds. Why and how plants produce diverse SLs are unknown. Here, cytochrome P450 CYP722C is identified as a key enzyme that catalyzes the reaction of BC-ring closure leading to orobanchol, the most prevalent canonical SL. The direct conversion of carlactonoic acid to orobanchol without passing through 4-deoxyorobanchol is catalyzed by the recombinant enzyme. By knocking out the gene in tomato plants, orobanchol was undetectable in the root exudates, whereas the architecture of the knockout and wild-type plants was comparable. These findings add to our understanding of the function of the diverse SLs in plants and suggest the potential of these compounds to generate crops with greater resistance to infection by noxious root parasitic weeds

A case of fulminant amebic colitis that could be saved

An 80-year-old man was admitted to a neighboring hospital with severe diarrhea and bloody stools. He did not have a remarkable medical history, was not homosexual, and had not traveled outside the country for several years. Colonoscopy was performed on the day of admission and revealed multiple ulcerations with edematous mucosa throughout the colorectum. Histopathological findings of biopsy specimen could not identify the reason for the inflamed colon. On postadmission day 6, the patient developed severe abdominal pain and underwent an emergent surgery for pan-peritonitis due to bowel perforation. The laparotomy revealed glossy fecal pan-peritonitis with perforation of the sigmoid colon; necrosis was observed through the entire length of the colon. The colonic tissue was extremely fragile and exhibited a blotting paper-like appearance. Total colectomy, sigmoid mucous fistula, ileostomy, and intraperitoneal drainage were performed. On postadmission day 12, histopathological findings of resected specimen raised the suspicion of amebic dysentery, and we accordingly treated him with metronidazole (2,250 mg/day) administered orally. Abdominal CT images taken on days 12 and 20 postadmission showed multiple liver abscesses, which improved following metronidazole administration. Metronidazole was discontinued 14 days after initiation as the patient’s general condition improved. His condition remained stable thereafter, and he was transferred two months after admission