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The synthesis of difluoromethylene-containing heterocycles was achieved via the palladium-catalyzed 1,1-difluoroallylation of heteronucleophiles followed by intramolecular Heck reaction. The allylic substitution of 3-bromo-3,3-difluoropropene was regioselectively accomplished by heteronucleophiles without rearrangement to give the corresponding 1,1-difluoroallylated compounds whose Heck cyclization proceeded in a 5-exo manner to afford ring-difluorinated indolines and dihydrobenzofurans. Their defluorinative allylic substitution further provided 2-fluoroindoles and 2-fluorobenzofurans.

A method for direct synthesis of tetrasubstituted fluoroarenes via nickel-catalyzed [2+2+2] cycloaddition is presented. The reaction combines one molecule of 1,1-difluoroethylene with two molecules of alkynes and involves sequential cleavage of the CF and CH bonds in difluoroethylene. The catalytic cycle is established by reduction of the intermediary NiII fluoride with a triethylborane-based borate.

Title zinc complex (II) is synthesized and applied to transition metal-catalyzed cross-coupling reactions with a wide range of organic halides yielding 2,2-difluorovinyl compounds.

Ketones and amides bearing difluoroallylic moieties undergo nucleophilic 5-endo-trig cyclization in the presence of KH or tBuOK as bases, a process considered to be disfavored according to the Baldwin rules.

3-Difluoromethylated 2,3-dihydrobenzoheteroles, 2,3-dihydrobenzofurans, 2,3-dihydrobenzothiophenes, and indolines were readily synthesized from ortho-heterosubstituted bromobenzenes, 2-bromophenols, 2-bromobenzenethiols, and 2-bromoanilines, respectively, in two steps: (1) γ-selective allylic substitution of 3-bromo-3,3-difluoropropene with heteronucleophiles and (2) intramolecular radical cyclization of the resulting 3,3-difluoroallylic compounds.

The nanoporous AuPd (AuPdNPore) alloy catalyst showed superior chemoselectivity and high catalytic activity for the direct 1,4-hydrosilylation of the conjugated cyclic enones with hydrosilane in comparison with the monometallic nanoporous Au and Pd catalysts. The enhanced catalytic properties of AuPdNPore arise mainly from the nanoporous structure and the synergistic effect of the AuPd alloy.

The title cation, generated in situ, is applied as an oxidant in the self-coupling of anilines, naphthols and the oxidative deprotection of Pmb-ethers.

Optimum reaction conditions are studied for both steps of the two-step synthesis of unsymmetrical 1,1-diaryl-2,2-difluoroethenes (V).

3,3-Difluoroallylic ketones readily undergo nucleophilic 5-endo-trig cyclization through their metal enolates to afford 5-fluor­inated 2-alkylidene-2,3-dihydrofurans. O-Cyclization exclusively occurred via intramolecular substitution of the vinylic fluorines.

A quaternary catalytic cobalt system promotes the hydroarylation of internal alkynes with aromatic imines through chelation-assisted C—H bond cleavage.

The presented reaction proceeds smoothly with sterically hindered triflates and halides with an excellent chemoselectivity for multihalogenated substrates (order of reactivity I < OTf < Br < Cl).

Chelation-controlled addition of arylpyridines or aromatic imines towards internal alkynes proceeds readily in the presence of a CoBr2—monophosphine catalyst to give tri-substituted olefins with high regio- and stereoselectivities in most cases.

Conversion of methane with carbon dioxide has been performed over seventeen metal oxides using a flow reaction system at 1123 K. The conversion ratio of carbon dioxide to methane is approximately two in most cases. Ethane and ethene (C 2 hydrocarbons) are formed over many oxides, and C 2 yield is higher over yttrium and manganese oxides. Rare earth catalysts such as yttrium, lanthanum, and samarium show higher C 2 selectivities of about 30%. C 2 selectivity is almost unchanged over yttrium and zirconium oxides during reaction while it decreases over samarium oxide. X-ray diffraction analysis reveals that some oxides such as manganese and iron oxides are reduced during reaction. The reaction mechanism for C 2 formation is discussed in terms of both adsorbed oxygen species dissociated from carbon dioxide and the lattice oxygen in metal oxides.

Spiders belonging to the genera, Nephila, Nephilengys, Araneus, etc., possess various polyamine toxins in their venom glands which paralyze insects by blocking the nerve-muscle signal transduction of glutaminergic synapses. More than 50 kinds of polyamine toxin analogs have been characterized which consist, in general, of the aromatic or heteroaromatic moiety connected with the combination of various types of polyamine chains. We are developing a new analytical system by means of a modern mass spectrometric technique which satisfies more rapid, highly sensitive and simple clean-up procedure without complicated chromatographic treatment. The trial of such approach has been performed by employing crude spider venom as the model material. This review article concerns with such proceeding of mass spectrometric analysis by microcolumn HPLC hyphenated FAB-MS system, continuous flow FAB-MS/MS system with high energy collision charge-remote fragmentation, solid and liquid matrix assisted laser desorption ionization (MALDI- and liquid MALDI-) technique connected with tandem mass spectrometer performing in the institute and in addition, femto-molar characterization of new spider venom spider polyamine toxins as a result of the application of such new techniques is addressed. Language: ja

Insulin resistance is a characteristic feature of type II diabetes as well as obesity. This insulin resistant state at the peripheral tissue level causes impaired glucose utilization, leading to hyperglycemia. Studies of antidiabetic agents by Takeda originated more than three decades ago when KK mice were introduced, followed by the development of a highly insulin-resistant animal model, KKAy mice. The first 2,4-thiazolidinedione derivative AL-321, which exhibited hypoglycemic effects in KKAy mice, was discovered by modification of the hypolipidemic agent AL-294 as a lead compound. Extensive structure-activity relationship studies on the analogues of AL-321 led to the selection of ciglitazone (ADD-3878) as a candidate for clinical evaluation. Ciglitazone, a prototypical compound in the series, was shown to normalize hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in various insulin-resistant animal models without altering normoglycemia in nondiabetic animal models. However, it appeared that a more potent compound was needed for further clinical evaluation of this class of compound. Further study of this series of compounds led to the finding of pioglitazone (AD-4833) as a promising clinical candidate. Pioglitazone clearly ameliorates the abnormal glucose and lipid metabolism in diabetic patients and was marketed in the USA in August 1999 for the treatment of type II diabetes. Pioglitazone is now marketed in more than 40 countries world wide. Historical aspects of our studies on pioglitazone and its biological activities are described.

The growth of undoped BaLiF 3 (BLF) single crystals, a candidate for window material in the vacuum-ultraviolet (VUV) region, was carried out in a Czochralski system under CF 4 atmosphere. BLF single crystals 1 inch in diameter were obtained and characterized. The thermal expansion coefficient of the BLF single crystal along the 〈100〉-axis was 3.33×10 −5 K. The distribution of birefringence along the 〈100〉-axis was in the order of 10 −7 . The absorption edge of BLF was determined to be 123 nm, showing high potential as an optical window material in the VUV region.

In screening for anti-MRSA antibiotics, novel lydicamycin congeners, TPU-0037-A, B, C and D, were isolated from a culture broth of an actinomycete strain. The producing strain, TP-A0598, was isolated from a seawater sample collected in Toyama Bay, Japan, and identified as Streptomyces platensis based on taxonomic characteristics. TPU-0037-A, B, C and D were purified by HP-20 resin, ODS column chromatographies and preparative HPLC, consecutively, and their structures were determined to be 30-demethyllydicamycin, 14,15-dehydro-8-deoxylydicamycin, 30-demethyl-8-deoxylydicamycin and 8-deoxylydicamycin, respectively, by NMR and MS analyses. The new congeners showed antibiotic activity against gram-positive bacteria including MRSA with the MIC of 1.56 to approximately 12.5 microg/ml.