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

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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.