Research Gland Stem Herba Siegesbeckiae Chemical Composition And Structural Modification Of The Active Ingredient

Plants of the Siegesbeckia pubescens Makino are annual herbs widely distributed in tropical and temperate zones.There are three species of Siegesbeckia and their aerial parts have been used as a traditional medicine to treat rheumatic arthritis, hypertension, malaria, neurasthenia and snake-bite in China. Previous pharmacological studies indicated that diterpeniod are the main bioactive constituents to rheumatic arthritis and a series of ent-kaurane and ent-pimarane diterpenoids have been isolated from Siegesbeckia species. Dautigenol is one of diterpenoids separated from Siegesbeckia species and pharmacological studies indicated that Dautigenol have the effect of anti-thrombotic.In order to search for novel lead compounds from Siegesbeckia pubescens Makino.we have conducted an in-depth study on Aerial part of Siegesbeckia pubescens Makino,at the same time, we modified the Dautigenol structure by reacted with a series of organic acids,for getting better bioavailability and pharmacokinetics lead compounds.In this thesis, the chemical constituents of the extracts with ethanol from Siegesbeckia pubescens Makino were studied,12compounds were isolated with silica gel, Sephadex LH-20and ODS,etc. On the basis of analysis with NMR,MS data and measuring of Physic-chemieal charaeters, the chemieal structures of12compounds were elucidated as:ent-3a,15,16-hydroperoxypimar-6,8(14)-diene(1),ent-3a,15β,16-hydroperoxypimar-8(14)-diene(2), ent-3α,15β,16,19-hydroperoxypimar-8(14)-diene(3),15,16-dihydroxy-4-norpimar-8(14)-3-one(4), Darutigeno (5),Kirenol(6),16β,17,18-tri-hydroxy-ent-kauran-19-oic acid(7), ent-17-hydroxy-16βH-kauran-19-oicacid(8),ent-16β,17-dihydroxy-kauran-19-oic acid(9),15,16-dihydroxipimar-8(14)-en-2-one(10),15,16-dihydroxipimar-8(14)-en-3-one (11), darutoside(12). Among them compounds1-4were new compounds.At the same time, to get better bioavailability and pharmacokinetics lead compo-unds. We modified the Dautigenol structure by a series of organic reactions and19terivatives were synthetized, among them14compounds were synthetized for the first time.Compounds isolated from Siegesbeckia pubescens Makino and the Dautigenol derivatives will be screened anti-thrombotic activities in vitro and vivo studies to find excellent lead compounds.