Molecular Design of Active Oxygen Scavengers Based on Chemical Reactivity of Vinylcyclopropanes

基于乙烯基环丙烷化学反应性的活性氧清除剂的分子设计

基本信息

批准号：
07672423
负责人：
KATAOKA Tadashi
金额：
$ 1.47万
依托单位：
Gifu Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

1. Synthesis of Vinylcyclopropane Derivatives : Dihydrothiopyran derivatives, prepared by cycloadditions of alpha-chloro sulfides with some 1,3-butadienes, were treated with a base to form the vinylcyclopropanes. We synthesized various vinylcyclopropane derivatives with captodative groups (an electron-withdrawing group and a sulfannyl group), in which some are spiro-bound with a 1,4-benzo-thiazin-3-one ring.2. Reactions of Vinylcyclopropane Derivatives : Reactions of the vinylcyclopropanes with p-toluenesulfonic acid caused the ring-opening of a cyclopropane and a novel 1,5-sulfanyl group rearrangement to give diene derivatives. Thermal reaction of benzothiazine-spiro-vinylcyclopropane afforded a ring-expanded product, benzo-thiazinone-spiro-cyclopentene. Benzenethiol radically added to the vinylcyclopropanes to give 4-phenylthiobut-2-enylbenzothiazinone. Radical reactions of the benzothiazinone-spiro-vinylcyclopropanes with oxygen, alkenes and alkynes were initiated by phenylselenyl radical, and gave dioxolanes, cyclopentenes and cyclopentadienes in good yields, respectively.3. In rabbit peritoneal polymorphonuclear leukocytes, the effect of the cyclopropane compounds on superoxide production was evalutated by chemiluminescence method using a specific superoxide probe, cypridina luciferin. Some compounds significantly inhibited superoxide generation induced by f-MLP in the dose dependent manner without change of viabilities and also suppressed active oxygen generation in a cell-free hypoxanthine-xanthine oxidase system. A series of the benzothiazinone vinylcyclopropane derivatives may be useful as a potentialscavenger of superoxide anion in vivo.

1。乙烯基环丙烷衍生物的合成：通过用α-氯硫化物的环加成和约1,3-丁二烯的二氢硫代基衍生物制备，并用碱处理以形成乙烯基环丙烷。我们通过贴贴基（一个吸引电子基团和一个磺基基团）合成了各种乙烯基环丙烷衍生物，其中有些人与1,4-苯并 - 硫嗪-3-3-ONE环的螺旋罗结合。2。乙烯基丙烷衍生物的反应：乙烯基环丙烷与p-二甲苯磺酸的反应导致环丙烷的环和新型1,5-硫烷基团重排以产生二烯衍生物。苯并噻嗪 - 螺旋乙烯基丙烷的热反应提供了环形膨胀的产物苯唑 - 噻唑酮-spiro-cyclopentene。从根本上添加到乙烯基环丙烷中，得到4-苯基噻卜-2-烯基苯甲噻嗪酮。苯噻唑氨酸 - 乙醇 - 乙烯基丙烷与氧，烷烃和炔烃的自由度反应是由苯基塞烯基自由基引发的，分别以良好的产量给出了二氧烷，环戊烯和环戊烯酸酯。3。在兔腹膜多形核白细胞中，使用特定的超氧化物探针Cypridina Luciferin评估了环丙烷化合物对超氧化物产生的影响。某些化合物显着抑制了F-MLP诱导的超氧化物的产生，而无需剂量变化，并且还抑制了无细胞的低黄嘌呤 - 黑明氨酸氧化酶系统中的活性氧产生。一系列的苯噻嗪酮乙烯基丙烷衍生物可能是体内超氧化物阴离子的潜在景观剂。