A validated HPLC‐fluorescence method with a semi‐micro column for routine determination of homocysteine,cysteine and cysteamine,and the relation between the thiol derivatives in normal human plasma

A semi‐micro column HPLC‐fluorescence method for routine determination of thiol derivatives such as homocysteine (Hcy), cysteine (Cys) and cysteamine (CA) is described. The thiol derivatives labeled with ammonium‐7‐fluorobenzo‐2‐oxa‐1,3‐diazole‐4‐sulfonate (SBD‐F) were isocratically separated within 12 min on a semi‐micro ODS column (Daisopak‐SP‐120‐5‐ODS‐BP) with a mixture of 25 mm acetate buffer (pH 2.00) and CH₃CN as a mobile phase. The purity and similarity of SBD‐thiols by a multi‐wavelength fluorescence detector were more than 92.3 and 96.7%. The detection limits of Hcy, Cys and CA at a signal‐to‐noise ratio of 3 were 0.16, 0.47 and 0.03 µm , respectively. Furthermore validation parameters such as accuracy, precision and robustness of the proposed method showed satisfactory results. Almost 850 plasma sample injections (range 572–1076, n = 3) for a column could be performed without differences in retention time and peak heights of labels. As an application of the proposed method, the determination of thiol derivatives in normal human plasma (n = 103) was demonstrated. The correlation coefficients between Hcy vs Cys and Hcy vs CA were 0.38 and −0.35, respectively. Copyright © 2009 John Wiley & Sons, Ltd.     

Preparation and characterization of organic–inorganic hybrids and coating films from 3‐methacryloxypropylpolysilsesquioxane

3‐Methacryloxypropylpolysilsesquioxane (MA‐PS) was prepared by acid‐ or base‐catalyzed hydrolytic polycondensation of 3‐methacryloxypropyltrimethoxysilane (MAS). MA‐PS coating film was prepared by dip‐coating on organic, metal and inorganic substrates, including poly(ethylene terephthalate), aluminum, stainless steel, and glass. The coating films on poly(ethylene terephthalate) and glass showed high adhesive strength. The hardness of coating films increased with increasing heat treatment temperature, whereas they decreased with increasing H₂O/MAS molar ratio. The refractive index of coating films increased with increasing heat treatment temperature. In addition, flat and transparent free‐standing films (0.24–0.27 mm thickness) were prepared from MA‐PS that were crack‐free after heat treatment at 1000 °C. Copyright © 2001 John Wiley & Sons, Ltd.     

Catalytic enantioselective Reissert-type reaction: development and application to the synthesis of a potent NMDA receptor antagonist (-)-L-689,560 using a solid-supported catalyst.

Full details of the first catalytic enantioselective Reissert-type reaction are described. Utilizing the Lewis acid-Lewis base bifunctional catalyst 5 or 6 (9 mol %), the Reissert products were obtained in 57 to 99% yield with 54 to 96% ee. Electron-rich quinolines produced better yields and enantioselectivities than electron-deficient substrates. Kinetic studies indicated that the reaction should proceed via the rate-determining acyl quinolinium formation, followed by the attack of a cyanide. The catalyst does not facilitate the first rate-determining step; however, it strongly facilitates the second cyanation step. The reaction was successfully applied to an efficient catalytic asymmetric synthesis of a potent NMDA receptor antagonist (-)-L-689,560. A key step is the one-pot process using the Reissert-type reaction from quinoline 1f, followed by stereoselective reduction of the resulting enamine 2f. This step gave the key intermediate 20 in 91% yield with 93% ee, using 1 mol % of 6. The enantiomerically pure target compound was obtained through 10 operations (including recrystallization) in total yield of 47%. Furthermore, 6 was immobilized to JandaJEL, and the resulting solid-supported catalyst 11 afforded 20 in a comparable yield to the homogeneous 6, but with slightly lower enantioselectivity.     

Synthesis and In Vitro Biological Evaluation of Psoralen‐Linked Fullerenes

Photodynamic therapy (PDT) is a widely used medicinal treatment for the cancer therapy that utilizes the combination of a photosensitizer (PS) and light irradiation. In this study, we synthesized two novel C₆₀ fullerene derivatives, compounds 1 and 2 , with a psoralen moiety that can covalently bind to DNA molecules via cross‐linking to pyrimidine under photoirradiation. Along with several fullerene derivatives, the biological properties of several novel compounds have been evaluated. Compounds 1 and 2 , which have been shown to induce the production of hydroxyl radicals using several ROS detecting reagents, induced DNA strand breaks with relatively weak activities in the in vitro detection system using a supercoiled plasmid. However, the psoralen‐bound fullerene with carboxyl groups ( 2 ) only showed genotoxicity in the genotoxicity assay system of the umu test. Compound 2 was also seen to have cytotoxic activities in several cancer cell lines at higher doses compared to water‐soluble fullerenes.     

Supernova neutrino nucleosynthesis of light elements with neutrino oscillations

Light element synthesis in supernovae through neutrino-nucleus interactions, i.e., the v process, is affected by neutrino oscillations in the supernova environment. There is a resonance of 13-mixing in the O/C layer, which increases the rates of charged-current -process reactions in the outer He-rich layer. The yields of 7Li and 11B increase by about a factor of 1.9 and 1.3, respectively, for a normal mass hierarchy and an adiabatic 13-mixing resonance, compared to those without neutrino oscillations. In the case of an inverted mass hierarchy and a nonadiabatic 13-mixing resonance, the increase in the 7Li and 11B yields is much smaller. Observations of the 7Li/11B ratio in stars showing signs of supernova enrichment could thus provide a unique test of neutrino oscillations and constrain their parameters and the mass hierarchy.     

Total synthesis of brevenal

The convergent total synthesis of brevenal, a non-toxic brevetoxin antagonist, has been achieved. The ABC ring segment and the E ring precursor were connected by the intramolecular allylation followed by ring-closing metathesis to furnish the pentacyclic ether compound. An alternative route to the key synthetic intermediate, a pentacyclic ether core, was also examined. The right- and left-hand side chains were introduced by Wittig and Horner-Wadsworth-Emmons reactions, respectively, to furnish brevenal (1).     

Stereocontrolled synthesis and structural confirmation of the C14-C24 degraded fragment of symbiodinolide

The C14-C24 fragment of symbiodinolide possessing the 17R/18R/21R absolute configuration, which was obtained as one of the degraded products of symbiodinolide, and its diastereomer possessing the 17R/18S/21R absolute stereochemistry were synthesized stereoselectively from cis-2-butene-1,4-diol, respectively. The detailed comparison of the synthetic products with the degraded product in the spectroscopic data confirmed unambiguously that the stereostructure of the C14-C24 fragment was 17R, 18R, and 21R.     

1,3-Dipolar cycloadditions of anhydro-5-hydroxyoxazolium hydroxide generated from 2-piperidinecarboxylic acid. Isolation of the primary adduct and synthesis of tetrahydroindolizines

1,3-Dipolar cycloaddition reactions of anhydro-5-hydroxyoxazolium hydroxide 3 generated from 2-piperidinecarboxylic acid and acetic anhydride, with dimethyl and diethyl acetylene-dicarboxylates, dibenzoylacetylene, p-benzoquinone, and 1,4-naphthoquinone gave the corresponding tetrahydroindolizines. In the case of the reaction with p-benzoquinone, the dihydroindolizine 12 was also formed. The primary N-bridged lactone intermediate 4 was isolated from the reaction of 2 with dibenzoylacetylene. Several attempted conversions of these tetrahydroindolizines into the corresponding aromatic indolizines were fruitless.