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

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的二氢噻喃衍生物用碱处理以形成乙烯基环丙烷。我们合成了各种带有吸电子基团和硫烷基的乙烯基环丙烷衍生物，其中一些化合物与1，4-苯并噻嗪-3-酮环螺键结合.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引起环丙烷的开环和新的1，5-硫烷基重排，得到二烯衍生物。苯并噻嗪-螺-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。苯乙烯与乙烯基环丙烷自由基加成，得到4-苯硫基丁-2-烯基苯并噻嗪酮。苯硒基自由基引发苯并噻嗪酮-螺乙烯基环丙烷与氧、烯烃和炔的自由基反应，分别以较好的产率得到二氧戊环、环戊烯和环戊二烯.在家兔腹腔多形核白细胞中，用超氧阴离子探针CypridinaEscherin化学发光法测定了环丙烷类化合物对超氧阴离子产生的影响。一些化合物显着抑制超氧化物的产生诱导的f-MLP在剂量依赖性的方式，而不改变的活力，也抑制活性氧的产生在无细胞的次黄嘌呤-黄嘌呤氧化酶系统。一系列苯并噻嗪酮乙烯基环丙烷衍生物有可能作为体内超氧阴离子清除剂。

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.