Short and flexible route to 3,4-diarylpyrrole marine alkaloids: syntheses of permethyl storniamide A, ningalin B, and lamellarin G trimethyl ether

A highly efficient route to 3,4-diarylpyrrole marine alkaloids has been developed using Hinsberg-type pyrrole synthesis and palladium-catalyzed Suzuki cross-coupling of the 3,4-dihydroxypyrrole bis-triflate derivatives as key reactions. Based on this approach, formal syntheses of permethyl storniamide A and ningalin B, and a total synthesis of lamellarin G trimethyl ether have been achieved.     

Novel ring transformation reactions of xanthine derivatives

The novel ring transformation reactions were found in the reactions of 1,3,7,9-tetra-alkyl-8,9-dihydroxanthines and acetylenic compounds. The reaction of the dihydroxanthine with DMAD gave a propellane type compound and with methyl propiolate afforded the similar type compound and a pyrimido[4,5-b]diazepine derivative. The mechanism of these reactions was also discussed.     

Ratiometric direct detection of nitric oxide based on a novel signal-switching mechanism

A novel fluorescent probe, which could be the first example of a ratiometric molecular probe for direct monitoring of NO production, has been developed using a 'spin-exchange' mechanism.     

Use of the tubulin bound paclitaxel conformation for structure-based rational drug design

A new computational docking protocol has been developed and used in combination with conformational information inferred from REDOR-NMR experiments on microtubule bound 2-(p-fluorobenzoyl)paclitaxel to delineate a unique tubulin binding structure of paclitaxel. A conformationally constrained macrocyclic taxoid bearing a linker between the C-14 and C-3'N positions has been designed and synthesized to enforce this "REDOR-taxol" conformation. The novel taxoid SB-T-2053 inhibits the growth of MCF-7 and LCC-6 human breast cancer cells (wild-type and drug resistant) on the same order of magnitude as paclitaxel. Moreover, SB-T-2053 induces in vitro tubulin polymerization at least as well as paclitaxel, which directly validates our drug design process. These results open a new avenue for drug design of next generation taxoids and other microtubule-stabilizing agents based on the refined structural information of drug-tubulin complexes, in accordance with typical enzyme-inhibitor medicinal chemistry precepts.     

Light emission from chlorine atoms formed in the dissociative excitation of HCI in a flowing afterglow of discharged argon

Light emission from Cl(5p) atoms (near 440 nm) produced in the reaction of HCl in a discharged flow of argon was investigated with a flowing-afterglow apparatus. Ionic species, most probably argon ions in metastable states, Ar^+M, were found to be responsible for the Cl(5p) production in the dissociative excitation of HCl.     

Improvement of in-gel digestion protocol for peptide mass fingerprinting by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

High-sensitivity, high-throughput analysis of proteins for proteomics studies is usually performed by polyacrylamide gel electrophoresis in combination with mass spectrometry. However, the quality of the data obtained depends on the in-gel digestion procedure employed. This work describes an improvement in the in-gel digestion efficiency for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) analysis. A dramatic improvement in the coverage of tryptic peptides was observed when n-octyl glucoside was added to the buffer. Whole cell extracted proteins from S. cerevisiae were separated by two-dimensional gel electrophoresis and stained with silver. Protein spots were identified using our improved in-gel digestion method and MALDI-TOFMS. In addition, the mass spectra obtained by using the matrix alpha-cyano-4-hydroxycinnamic acid (CHCA) were compared with those obtained using 2,5-dihydroxybenzoic acid (DHB). The DHB matrix usually gave more peaks, which led to higher sequence coverage and, consequently, to higher confidence in protein identification. This improved in-gel digestion protocol is simple and useful for protein identification by MALDI-TOFMS.     

Synthesis and thermolysis of N-heteroarylacetylazides and α-oximino-α-(N-heteroaryl)acetylazides

Treatment of N-heteroarylacethydrazides with an equimolar amount of nitrous acid afforded N-heteroaryacetylazides and subsequent thermolysis of these azides gave the analogues of 2,3-dihydroimidazo[1,5-a]pyridin-3-one. When some of these cyclized compounds were treated with nitrous acid, the ring opening reaction occurred and recyclized 3-(N-heteroaryl)-1,2,4-oxadiazolin-5-ones were obtained. Treatment of N-heteroarylacethydrazides with two equivalent moles of nitrous acid afforded α-oximino-α-(N-heteroaryl)acetylazides. Thermolysis of these azides gave mixtures of 3-(N-heteroaryl)-1,2,4-oxadiazolin-5-one and 3-hydroxy-4-(N-heteroaryl)furazan. On the basis of the effects of heterocyclic rings and solvents upon the relative yield of two types of the products, one plausible mechanistic explanation for the decomposition of such azides was proposed. α-Oximino-α-(H-heteroaryl)acetylazides were converted into cyano N-heterocycles by the action of alkali in good yields.     

Rapid determination of 89Sr and 90Sr in radioactive waste using Sr extraction disk and beta-ray spectrometer

A rapid determination method in which beta-ray spectrometry was combined with solid phase extraction using Sr Rad Disk was developed for the determination of ⁸⁹Sr and ⁹⁰Sr in low-level radioactive waste. Various amounts of ⁸⁹Sr, ⁹⁰Sr, and ⁹⁰Y retained by the Sr Rad Disk was measured by a beta-ray spectrometer, and it was found that both ⁸⁹Sr and ⁹⁰Sr were simultaneously determined with <30% error (2σ) at ⁸⁹Sr/⁹⁰Sr radioactivity ratio of 0.3 to 45. The present method was successfully applied to actual radioactive liquid waste samples arising from nuclear facilities in Japan Atomic Energy Agency. Strontium was simply separated from interfering nuclides such as ¹³⁷Cs and ¹⁵⁴Eu, and matrix components by the Sr Rad Disk, and the results obtained by beta-ray spectrometry was in good agreement with that of the conventional analysis.     

Novel 2-pyrone synthesis via the nucleophilic addition of active methine compounds to 2-alkynone

Novel 2-pyrone synthesis via the nucleophilic addition of active methine compounds to 2-alkynone has been developed. The reaction of active methine compounds with 2-alkynone provided 2-pyrones in good yields.     

Fluorescent Molecular Recognition and Sensing System of Bis-Dansyl Modified γ-Cyclodextrins

Flexible hosts, 6A,6B-; 6A,6C-; 6A,6D-; and 6A,6E-bis dansylglycine-modified -cyclodextrins (-1, -2, -3, and -4, respectively) have been synthesized as a sensing molecule for organic guests including terpenoids and bile acids. These host compounds show a pure monomer fluorescence whose intensity is decreased or enhanced upon addition of guest species. The value I/I₀, where I and I₀ are fluorescence intensities in the presence and absence of a guest and I is I₀- I, was used as a parameter of sensitivity. These hosts exhibit highly sensitive and selective molecular recognition ability, particularly, for lithochoic acid, chenodeoxycholic acid, and ursodeoxycholic acid. The behaviors of the appended moieties of these hosts when host–guest complexation occurs are studied by induced circular dichroism (ICD) spectra and fluorescence spectral change on accommodation of a guest. The ICD pattern of these hosts alone or on accommodation of a guest is very similar, indicating that the behavior of the appended moieties are very similar. The guest-induced variations in the fluorescence or ICD intensity suggest that the appended moieties act as a hydrophobic cap that enables the cyclodextrin to form 1 : 1 host–guest complexes.