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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672423/
• 关键词: vinylcyclopropane; sulfonium salt; sulfur ylide; sulfur heterocycle; active oxygen scavenger; 硫黄イソド; 活性酸素

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-酮环通过螺环连接.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。

项目成果

Tadashi Kataoka: "Synthesis and Reactions of Lactam Sulfonium Salts with a Sulfonio Bridgehead. II." Chem.Pharm.Bull.45. 265-271 (1997)

Tadashi Kataoka：“内酰胺锍盐与磺桥头的合成和反应。II。”

Tadashi Kataoka: "Generation and Reactions of Butadienylthionium Ions from 2-Vinylcyclopropyl Sulfoxides under Pummerer Conditions" J.Chem.Soc., Perkin Trans.1. 737-739 (1995)

Tadashi Kataoka：“Pummerer 条件下 2-乙烯基环丙基亚砜中丁二烯基硫鎓离子的生成和反应”J.Chem.Soc.，Perkin Trans.1。

Hiroshi Shimizu: "Ring Transformatoin of the Adducts of the Polar Cycloadditions of 2-Benzo-thiopyrylium Salts" J.Chem.Soc., Perkin Trans.1. 1583-1589 (1995)

Hiroshi Shimizu：“2-苯并-噻吩鎓盐极性环加成加合物的环变换”J.Chem.Soc.，Perkin Trans.1。

Tasashi Kataoka: "Synthesis and Reactions of Lactam Sulfonium Salts with a Sulfonio Bridgehead. II." Chem. Pharm. Bull.45. 265-271 (1997)

Tasashi Kataoka：“内酰胺锍盐与磺桥头的合成和反应。II。”

Tadashi Kataoka: "Acid-promoted C_1-C_2 Bond Fission and Subsequent 1,5-Sulfenyl Shift of 1-Acceptor-1-sulfenyl-substituted 2-Vinyl-" Chemistry Letters. 459-460 (1995)

Tadashi Kataoka：“酸促进的 C_1-C_2 键裂变和随后的 1-受体-1-硫基取代的 2-乙烯基-的 1,5-硫基转移”化学快报。