Polycyclic N-Hetero Compounds. XL. Reaction of Cyclic Ketones with Trisformylaminomethane

Reactions of cyclic ketones such as α-tetralone, 1,3-cyclohexanedione, or naphthalenedione with formamide or trisformylaminomethane (TFAM) have shown to form polyclic fused pyrimidines by us. Reactions of terpene ketones like l-menthone, d-camphor, l-carvone with TFAM were performed, and 8-isopropyl-5-methyl-5,6,7,8-tetrahydroquinazoline, borno[2,3-d] pyrimidine, and 5-isopropenyl-8-methyl-5,6-dihydroquinazoline were expectedly obtained from three terpenes. Minor products of 5-isopropenyl-8-methyl-5,6,7,8-tetrahydroquinazoline and 5-isopropenyl-8-methylquinazoline were formed with 5-isopropenyl-8-methyl-5,6-dihydroquinazoline by disproportionation reaction of l-carvone. Furthermore, No-formylmenthylamine, N-formylbornylamine, and N-formylcarvylamine were obtained as the Leuckart-type products terpene ketones in these reactions. The reaction of N-benzyl-4-piperidone with TFAM gave desired 6-benzyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. The reaction of diethyl succinylsuccinate with TFAM afforded tricyclic 4,9-dioxo-3,4,8,9-tetrahydropyrimido[4,5-g]quinazoline. Above compounds were determined by the measurements of their instrumental analyses.α-テトラロン、1,3-シクロヘキサンジオン、ナフタレンジオン等の環式ケトン類とホルムアミド或はトリスホルミルアミノメタン（TFAM）との反応により、多環式縮合ピリミジン誘導体を容易に合成できる事は既に報告した。この反応の一環として環式ケトンにl-メントン、d-カンファ、l-カルボン等の生理活性を有するテルペンケトン及びN-ベンジル-4-ピペリドンとジエチルサクシニルサクシネートを用いてTFAMとの反応を検討した。3種のテルペンケトン類からは予期した縮合ピリミジンとして8-イソプロピル-5-メチル-5,6,7,8-テトラヒドロキナゾリン（Ⅱ）、ボルノ[2,3-d]ピリミジン（Ⅴ）、及び5-イソプロペニル-8-メチル-5,6-ジヒドロキナゾリン（Ⅷ）を得た。Ⅷの分離の際にⅧの不均化合物である5-イソプロペニル-8-メチル-5,6,7,8,-テトラヒドロキナゾリン（Ⅸ）及び5-イソプロペニル-8-メチルキナゾリン（Ⅹ）の生成をGC-MS及びpmrで確認したが、それらの単離には到らなかった。又、テルペンケトン類からLeuckart型反応生成物と考えられるN-ホルミルメンチルアミン（Ⅲ）、N-ホルミルボルニルアミン（Ⅵ）及びN-ホルミルカルビルアミン（ⅩⅠ）を得た。N-ベンジル-4-ピペリドンとTFAMとの反応では、6-ベンジル-5,6,7,8-テトラヒドロピリド[4,3-d]ピリミジン（ⅩⅢ）が得られた。最後に、環式ジケトンジエステルであるジエチルサクシニルサクシネートとTFAMとの反応に於いては一挙に三環性の4,9-ジオキソー3,4,8,9-テトラヒドロピリミド[4,5-g]キナゾリン（ⅩⅤ）を得ることが出来た。得られた化合物の構造はir,mass,pmr,元素記号等で決定した

Flow Injection Analysis for Hydrogen Peroxide in Environmental Waters

先に開発した過酸化水素のフローインジェクション分析法（FIA）のシステムや触媒カラムに詳細な検討を加え，ppbレベルの過酸化水素の定量法を開発した。また，本研究で得られたFIAを用いて，57～944ppbになるように過酸化水素を雨水に添加し，回収実験を行った。その結果，回収率と再現性とも良好で，化学発光法より優れていた。なお，FIAでの検出下限は，約10ppbであった。We tried to determine a low-level hydrogen peroxide by using a flow injection analysis (FIA) which was reported in our previous paper. For this purpose, the constituents of the system including the catalytic column were re-examined in detail. As the result, we developed a new system of the FIA which is available for the determination of ppb-order hydrogen peroxide. When hydrogen peroxide spiked in rain-waters(57-944ppb)was analyzed by the FIA, better recovery and reproducibility were attained compared to chemiluminescent analyses. The lower-limit of determination was 10 ppb hydrogen peroxide

ω-Carboxyl variants of 7-ketocholesteryl esters are ligands for β2-glycoprotein I and mediate antibody-dependent uptake of oxidized LDL by macrophages

beta(2)-Glycoprotein I (beta(2)-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome. We recently reported that beta(2)-GPI specifically binds to oxidized LDL (oxLDL) and that the beta(2)-GPI's major ligand, oxLig-1 is 7-ketocholesteryl-9-carboxynonanoate (Kobayashi, K, E. Matsuura, Q. P. Liu, J. Furukawa, K. Kaihara, J. Inagaki, T. Atsumi, N. Sakairi, T. Yasuda, D. R. Welker, and T. Koike. 2001. A specific ligand for beta(2)-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages. J Lipid Res. 42: 697-709). In the present study, we demonstrate that omega-carboxylated 7-ketocholesteryl esters are critical for beta(2)-GPI binding. A positive ion mass spectrum of a novel ligand, designated oxLig-2, showed fragmented ions at m/z 383 and 441 in the presence of acetone, which share features of oxLig-1 and 7-ketocholesterol. In the negative ion mode, ions at m/z 627, 625, and 243 were observed. oxLig-2 was most likely 7-ketocholesteryl-12-carboxy (keto) dodecanoate. These ligands were recognized by beta(2)-GPI. Liposome binding to macrophages was significantly increased depending on the ligand's concentration, in the presence of beta(2)-GPI and an anti-beta(2)-GPI Ab. Synthesized variant, 7-ketocholesteryl-13-carboxytxidecanoate (13-COOH-7KC), also showed a significant interaction with beta(2)-GPI and a similar binding profile with macrophages. Methylation of the carboxyl function diminished all of the specific ligand interactions with beta(2)-GPI. Thus, omega-carboxyl variants of 7-ketocholesteryl esters can mediate anti-beta(2)-GPI Ab-dependent uptake of oxLDL by macrophages, and autoimmune atherogenesis linked to beta(2)-GPI interaction with oxLDL