The efficient synthesis of d-xylulose and formal synthesis of Syringolide 1

Wittig reaction and asymmetric dihydroxylation were used as the key steps in the synthesis of D-xylulose, a commercially available but costly carbohydrate. The effects of protecting groups and reactions conditions on asymmetric dihydroxylation are demonstrated. Optically pure D-xylulose was obtained after 4-6 steps from readily available hydroxyacetone and ethylene glycol. The method also involves some other valuable intermediates along the synthesis. Those intermediates were applied in the formal synthesis of Syringolides. A key precursor butenolide to Syringolide 1, the first non-proteinaceous specific elicitors of plant hypersensitive response, was obtained after 3 steps from the intermediate (8–10 steps from hydroxyacetone and ethylene glycol). Wittig reaction and asymmetric dihydroxylation were used as the key steps in the synthesis of D-xylulose, a commercially available but costly carbohydrate. The effects of protecting groups and reactions conditions on asymmetric dihydroxylation are demonstrated. Optically pure D-xylulose was obtained after 4-6 steps from readily available hydroxyacetone and ethylene glycol. The method also involves some other valuable intermediates along the synthesis. Those intermediates were applied in the formal synthesis of Syringolides. A key precursor butenolide to Syringolide 1, the first non-proteinaceous specific elicitors of plant hypersensitive response, was obtained after 3 steps from the intermediate (8–10 steps from hydroxyacetone and ethylene glycol)

Ultrasound assisted one-pot synthesis of benzo-fused indole-4, 9-dinones from 1,4-naphthoquinone and α-aminoacetals

A one-pot synthesis of benzo[f]indole-4,9-diones from 1,4-naphthoquinone with α-aminoacetals has been developed. This method provides a straightforward synthesis of benzo[f]indole-4,9-diones via intramolecular nucleophilic attack of aminoquinones to aldehydes under mild reaction conditions. The detailed mechanism was also investigated

Lifestyle Habits Adjustment for Hypertension and Discontinuation of Antihypertensive Agents

Background: Hypertension is one of lifestyle-related diseases, and prevention and effect of reduction pressure can be expected by non-pharmacological interventions. Authors have continued guidance of adjustment for lifestyle to thousands of hypertensive patients, resulting 4.6%-6.1% case could discontinue hypertensive agents. This study enrolled patients with all necessary related data. Subjects and methods: Subjects were 50 patients with hypertension (M/F: 25/25, age 65.4 ± 8.6 vs. 53.4 ± 6.2 years, BMI 23.4 ± 2.7 vs. 22.3 ± 2.5, respectively), who could discontinued antihypertensive agents. They received consultation and intervention from registered dietitian nutritionists, exercise therapists and nurses. Results: The comparative results on males and females are as follows: smoking habit was 76% vs. 0%, alcohol intake was 60% vs. 0%, diabetes complication was 16% vs. 8%, and hyperlipidemia was 32% vs. 52%, respectively. These cases showed rare to none incidence of cerebral vascular accident (CVA), coronary heart disease (CHD) and chronic kidney disease (CKD). Consultations in median were 4.0 vs. 4.0 times, median weight reduction was 2.2 kg vs. 1.6 kg and median period withdrawal of the drug was 2.0 years vs. 2.5 years. Discussion and conclusion: When living adjustment is advised, blood pressure decreases due to behavior change. Our results suggest that these cases have less arteriosclerosis development, which enables withdrawal of medicine. It is necessary to carefully observe the progress whether the antihypertensive drug will be unnecessary or will be restarted. Current results obtained would become the fundamental data in the future, and the adjustment for diet and exercise would be useful for more adequate treatment for hypertension

Solar Synthesis of Acyl hydroquinones and their Bioactivity.

Without the Sun, we would not enjoy the benefits of life here on the Earth. This energy is essential and crucial for sustaining life: playing important roles in circadian rhythms and photosynthesis in plants. In our research, this endlessly renewable clean energy source is utilized for photo-Friedel-Crafts acylation of 1,4 - benzoquinones and 1,4 - naphthoquinones. Photo-Friedel-Crafts acylation was first discovered in 1891 and although there have been reported examples of acylated products, the substrates are still limited. In this project a variety of aldehydes having different substituents are examined, and bioassays were performed. While conventional methods for photochemistry use artificial UV light, replacement with solar radiation would yield no energy expense. Exposing a reaction mixture of 1,4-benzo or naphtho quinone with an aldehyde to direct sunlight gave acylated hydroquinones, compounds which serve as important intermediates for pharmaceuticals. Two products were evaluated for their anticancer activities against MCF-7 and MDA-MB-231 human breast cancer cells by MTS assay. CC50 values indicate that one of these compounds displays strong inhibitory activities against both tumor cell lines. These two compounds were also examined in a Luciferase assay using a parasitic protozoan, Giardia lamblia, the results demonstrated that one of them possesses anti-giardial activity. This is interesting because the difference between the two compounds is with/without one oxygen atom. These results encouraged us to elaborate the structure–activity relationship and find drug–receptor interactions. We will also synthesize more compounds with different substituents to study biological activity

One-pot γ-Amino Acids Synthesis from CO2 via Zirconacycle

One-pot γ-amino acids synthesis from CO2 via zirconacycle was studied. It has been reported that ketone and isocyanides are viable substrates for insertion into Zr‒C bonds of zirconocene‒1-aza-1,3-diene complexes. The purpose of this project is to explore the viability of CO2 insertion to develop a new method for γ-amino acids synthesis in which all the reactions are executed in a single pot. In this method, first zirconocene‒1-aza-1,3-diene complex is prepared by using Cp2Zr2Cl2 and an α, β-unsaturated imine. Second, CO2 was introduced into the zirconocene complex solution to form the seven-membered ring which indicates a successful insertion of CO2 and it is characterized by NMR spectroscopy. Finally, to obtain γ-amino acids the hydrolysis condition for cleavage of Zr‒O and Zr‒N bonds will be investigated. This method will prove the viability of CO2 insertion into zirconium complexes and the utility of this zirconocene‒1-aza-1,3-diene complex for one-pot γ-amino acids synthesis

Synthesis of Methylene γ-lactones Using Carbon Dioxide

Many industrial processes generate the greenhouse gas, carbon dioxide, as a byproduct. Carbon dioxide can be captured and recycled by using it in organic synthesis to prepare beneficial compounds. The goal of this project is to develop a new method of synthesizing methylene γ-lactones using CO2-metal complexes. Many gamma lactones are biologically active, and their synthesis is of importance to pharmaceutical and other industries. Allenes can react with a transition metal-CO2 complex. It is proposed that a titanium metal complex prepared with an aldehyde will bind to an allene, and a seven-membered ring forms as CO2 is inserted at the titanium-carbon bond. Subsequent intramolecular rearrangement affords a methylene γ-lactone when the oxygen atom associated with the organic substrate acts as a nucleophile and cleaves the titanium-oxygen bond. Recapturing carbon dioxide emission and using it in organic synthesis is a potential method for reducing the release of a harmful greenhouse gas into the environment, and a way to recycle carbon that would be wasted otherwise

Niclosamide induces protein ubiquitination and inhibits multiple pro-survival signaling pathways in the human glioblastoma U-87 MG cell line

<div><p>Glioblastoma is the most common and lethal malignant primary brain tumor for which the development of efficacious chemotherapeutic agents remains an urgent need. The anti-helminthic drug niclosamide, which has long been in use to treat tapeworm infections, has recently attracted renewed interest due to its apparent anticancer effects in a variety of <i>in vitro</i> and <i>in vivo</i> cancer models. However, the mechanism(s) of action remains to be elucidated. In the present study, we found that niclosamide induced cell toxicity in human glioblastoma cells corresponding with increased protein ubiquitination, ER stress and autophagy. In addition, niclosamide treatment led to down-regulation of Wnt/β-catenin, PI3K/AKT, MAPK/ERK, and STAT3 pro-survival signal transduction pathways to further reduce U-87 MG cell viability. Taken together, these results provide new insights into the glioblastoma suppressive capabilities of niclosamide, showing that niclosamide can target multiple major cell signaling pathways simultaneously to effectively promote cell death in U-87 MG cells. Niclosamide constitutes a new prospect for a therapeutic treatment against human glioblastoma.</p></div