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α-氯硫化物与一些1,3-丁二烯的环加成制备二氢噻喃衍生物，用碱处理形成乙烯基环丙烷。我们合成了多种带有捕获基团（吸电子基团和硫烷基）的乙烯基环丙烷衍生物，其中一些衍生物与1,4-苯并噻嗪-3-酮环进行螺键连接。 2．乙烯基环丙烷衍生物的反应：乙烯基环丙烷与对甲苯磺酸的反应导致环丙烷开环和新型1,5-硫烷基重排，得到二烯衍生物。苯并噻嗪酮-螺环乙烯基环丙烷的热反应得到扩环产物苯并噻嗪酮-螺环戊烯。苯硫醇自由基加成到乙烯基环丙烷上，得到4-苯硫基丁-2-烯基苯并噻嗪酮。苯基硒基自由基引发苯并噻嗪酮螺环乙烯基环丙烷与氧、烯烃和炔烃发生自由基反应，分别以良好的产率生成二氧戊环、环戊烯和环戊二烯。 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，通过化学发光方法评估了环丙烷化合物对超氧化物产生的影响。一些化合物以剂量依赖性方式显着抑制由f-MLP诱导的超氧化物产生，而不改变活力，并且还抑制无细胞次黄嘌呤-黄嘌呤氧化酶系统中活性氧的产生。一系列苯并噻嗪酮乙烯基环丙烷衍生物可用作体内超氧阴离子的潜在清除剂。