Total Synthesis of Gambierol by Using Oxiranyl Anions

Gambierol was isolated as a neurotoxin from the cultured cells of the ciguatera causative dinoflagellate Gambierdiscus toxicus and classified as a member of the polycyclic ether family of marine toxins. The structure consists of a ladder‐shaped trans‐fused octacyclic ring system that includes 18 stereogenic centers, two 1,3‐diaxial dimethyl‐substituted tetrahydropyranyl rings, and a partially conjugated triene side chain. The total synthesis of gambierol has been achieved by utilizing an oxiranyl anion strategy in an iterative manner. Synthetic highlights of this route include direct carbon–carbon formation on epoxides, sulfonyl‐assisted 6‐endo cyclization, and an expansion reaction of the tetrahydropyranyl rings to oxepanes to forge the polycyclic architecture of the target molecule.     

A nonparametric method of multi-step ahead forecasting in diffusion processes

This paper provides a nonparametric model of multi-step ahead forecasting in diffusion processes. The model is constructed from the local linear model with the Gaussian kernel. The paper provides simulation studies to evaluate its performance of multi-step ahead forecasting by comparing with the global linear model, showing the better forecasting performance of the nonparametric model than the global linear model. The paper also conducts empirical analysis for forecasting using intraday data of the Japanese stock price index and the time series of heart rates. The result shows the performance of forecasting does not differ much in the Japanese stock price index, but that the nonparametric model shows significantly better performance in the analysis of the heart rates.     

Electrochemical extraction of proteins by reverse micelle formation

The transfer of proteins by the anionic surfactant bis(2-ethylhexyl) sulfosuccinate (AOT) at a polarized 1,2-dichloroethane/water (DCE/W) interface was investigated by means of ion-transfer voltammetry. When the tetrapentylammonium salt of AOT was added to the DCE phase, the facilitated transfer of certain proteins, including cytochrome c (Cyt c), ribonuclease A, and protamine, could be controlled electrochemically, and a well-defined anodic wave for the transfer was obtained. At low pH values (e.g., pH 3.4), the anodic wave was usually well-separated from the wave for the formation of protein-free (i.e., unfilled) reverse micelles. The anodic wave for the protein transfer was analyzed by applying the theory for facilitated transfer of ions by charged ligands and then supplying information regarding the number of AOT anions reacting with one protein molecule and the total charge carried by the protein transfer. However, controlled-potential electrolyses performed for the transfer of Cyt c, which is red, revealed that the protein-AOT complexes were unstable in DCE and liable to aggregate at the interface when the pH of the W phase was 3.4. At pH 7.0, when formation of unfilled reverse micelles occurred simultaneously, the protein-AOT complexes appeared to be stabilized, probably via fusion with unfilled reverse micelles.     

Electron spin resonance studies on the oxidation mechanism of sterically hindered cyclic amines in TiO2 photocatalytic systems

A sterically hindered cyclic amine, 4-hydroxy-2,2,6,6-tetramethylpiperidine (HTMP), is converted to the corresponding aminoxyl radical (nitroxide radical), 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl (TEMPOL radical) as a result of a photocatalytic reaction in TiO2 aqueous suspension. The time profile of the radical formation and the effect of additives, such as SCN-, I-, methanol, and H2O2, on the initial formation rate were measured in order to elucidate the reaction mechanism. The experimental observations indicated that the direct photocatalytic oxidation of HTMP followed by reaction with O2 is the dominant process in the formation of TEMPOL radicals. Electrochemical measurements showed that HTMP is oxidized at 0.7 V (vs NHE), which is consistent with the proposed mechanism. The possibility of other processes, involving reactions with singlet molecular oxygen, superoxide radical, and hydroxyl radical, were excluded from the reaction mechanism.     

Determination of the purity of acidimetric standards by constant-current coulometry, and the intercomparison between CRMs

The accuracy and uncertainty of the coulometric measurement results of reference materials for acidimetric titration were examined in this study. The results for amidosulfuric acid and potassium hydrogen phthalate are presented. The uncertainty was investigated by examining the dependency on the sample size and on the electrolysis current. Changes in the titration parameters did not result in any significant effects on the titration results. Acidimetric standards with the certified value linked to the SI were developed. In addition, the intercomparison of acidimetric standards was carried out by gravimetric titration, and the relationship between our coulometric results was determined. Furthermore, due to recent internationalization, not only the traceability to the SI but also the relationship and consistency of their analytical data have gained increasing importance. Our results were validated using certified reference materials (CRMs) obtained from different National Metrology Institutes (NMIs), and their relationships are presented. Presented at -- “BERM-10” -- April 2006, Charleston, SC, USA.     

Stability analysis of the two rotational isomers of meta-fluorobenzaldehyde in the S0, S1, and S2 electronic states

For a determination of the stabilization energy between the two rotational isomers of m-fluorobenzaldehyde, the S(1,2)<--S0 absorption spectra were observed in fluid n-hexane solutions at 293 and 198 K. After employing a simulation method for the spectra, we succeeded in determining the stabilization energies in the ground and the relevant excited state at the same time. The energy was estimated to be 1.7 +/- 0.5 kJ mol(-1) for S0 and also for S1 while it was 2.9 +/- 0.5 kJ mol(-1) for S2. Ab initio calculations at MP2/6-311G** computational level predicted that the O-cis form in the S0 state is more stable by 1.9 +/- 0.5 kJ mol(-1) than the counterpart rotamer, O-trans form. In summary, a schematic energy level diagram of the two rotational isomers will be illustrated for the S0, S1, and S2 states in the fluid system.     

Synthesis of the C8-C20 and C21-C30 segments of pectenotoxin 2

In this study, we synthesized the C8-C20 and C21-C30 segments of the diarrhetic shellfish toxin pectenotoxin 2. The C8-C20 segment was assembled from a phosphonate corresponding to the C8-C15 segment (prepared from l-malic acid in 19 steps) and an aldehyde corresponding to the C16-C20 segment (synthesized from 3-methyl-3-butenol in nine steps) by a twelve-step process including the Horner-Wadsworth-Emmons reaction, regio- and stereoselective reduction of the resulting enone, diastereoselective epoxidation, and 5-exo epoxide cleavage forming the C-ring. The C21-C30 segment was constructed in 13 steps from (S)-glycidol via a route involving E-ring formation by 5-exo epoxide cleavage and stereoselective methylation at C27 by the Evans method.     

First total synthesis of a novel monoterpenoid isoquinoline alkaloid, (+/-)-alangine

The structure including the stereochemistry of a novel monoterpenoid isoquinoline alkaloid, alangine, was confirmed by total synthesis via N-acyliminium cyclization to construct the isoquinoline skeleton and reductive cleavage of vinyl epoxide with Pd(0) catalyst.     

Optical Sensing by Silica/Titania Thin Films Doped with Oxacarbocyanine Dye

Photocurrent responses of sol-gel films of silica/titania doped with oxacarbocyanine dye were investigated with a sandwich-type photocell constructed with polymer electrolyte membrane and indium-tin-oxide glass electrodes. At an equilibrium and positive bias voltages, a typical photocell exhibited negative and positive current peaks when the visible light illumination was on and off, respectively. The wavelength dependence of the photocurrent responses well matched to the absorption band of the doped dye. This differential photocurrent response was attributed to trapping of carriers photoexcited in the dye molecules at the defect states in the matrix film. At negative bias voltages, on the other hand, the cell exhibited constant, negative photoelectrochemical currents under illumination. These differential and linear photocurrent responses were affected by the SiO₂/TiO₂ matrix structures depending on the Si : Ti ratio.     

Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents

Flavonoids are polyphenols with broad known pharmacological properties. A series of 2,3-dihydroflavanone derivatives were thus synthesized and investigated for their anti-inflammatory activities. The target flavanones were prepared through cyclization of 2′-hydroxychalcone derivatives, the later obtained by Claisen–Schmidt condensation. Since nitric oxide (NO) represents an important inflammatory mediator, the effects of various flavanones on the NO production in the LPS-induced RAW 264.7 macrophage were assessed in vitro using the Griess test. The most active compounds were flavanone (4G), 2′-carboxy-5,7-dimethoxy-flavanone (4F), 4′-bromo-5,7-dimethoxy-flavanone (4D), and 2′-carboxyflavanone (4J), with IC50 values of 0.603, 0.906, 1.030, and 1.830 µg/mL, respectively. In comparison, pinocembrin achieved an IC₅₀ value of 203.60 µg/mL. Thus, the derivatives synthesized in this work had a higher NO inhibition capacity compared to pinocembrin, demonstrating the importance of pharmacomodulation to improve the biological potential of natural molecules. SARs suggested that the use of a carboxyl-group in the meta-position of the B-ring increases biological activity, whereas compounds carrying halogen substituents in the para-position were less active. The addition of methoxy-groups in the meta-position of the A-ring somewhat decreased the activity. This study successfully identified new bioactive flavanones as promising candidates for the development of new anti-inflammatory agents.