Pyrrolizidine Alkaloid OH Pyrrolizidine Pyrrolizidine Alkaloids,PA Queen butterfly 吡咯里西啶类生物碱的毒性是源于其分子可以在体内一些酶的作用下失去两 个氢原子，成为含不饱和吡咯环的中间产物，这种中间产物是强烈的亲电烷基化 试剂，可以和细胞的代谢产物以至DNA、蛋白质反应，因此具有细胞毒性和致癌 性。吡咯里西啶类生物碱对肝脏的损害尤为明显，常见急性中毒症状是肝小静脉 闭塞症，严重者可导致肝硬化、腹水直至死亡。慢性中毒症状则是肝硬化，与黄 曲霉毒素、乙肝病毒可发生协同作用，可能导致原发性肝癌。 自然界约3%的开花植物都含PA,所以也有约3%的蜂蜜含PA
Piperidine Alkaloids enecionine No ocrotaline N-oxide 千里光一吡略啶 Phalaenopsine N-oxide Lycopsamine Noxide Senecio madagascariensis (Fireweed) camel belly 骆驼肚子 May 2008,190 people were affected and 17 had died from liver failure in Afghanistan
Pyrrolizidine Alkaloid Erucifoline N-oxic Eruciflorine N-oxide Senkirkine Jacobine N-oxide Examples of PAs found in Senecio species.Senecionine N-oxide is the basic structure from which other PAs are formed.These senecionine type PAs have an otonecine (senkirkine)or retronecine ester base (e.g.,senecionine)and a 12- membered macro-cyclic ring.Phytochem Rev(2011)10:75-82
Metabolic oxidation pathways of retronecine-type and otonecine-type PAs HC一DNA Necic acid Genotoxicity Pyrrole-DNA adducts Necine base Oxidation P450 Retronecine-type HaC-Proteir adduct Hepatotoxicity Pyrrole-protein adducts H are pyrrole moiety Dehydro-PAs Acidified ethanolic dative N-de AgNO HC-OCH2CH3 H.CH.CCo H2C-OCH2CH Otonecine-type hylaminobenzaldehyd 同=N 7.9-di-ethoxy-DHP-3-DABA 7,9-di-ethoxy-DHP 2estrpaoomst1non Mass spectrometry analysis The five major structural types of pyrrolizidine alkaloids.In plants, these alkaloids occur mostly in form of their N-oxides
凶险的剧毒天然产物 -OH HO-OH D-Glc OH D-Gal OH L-Rha OT HO CH3 龙葵碱Solanine HO Vladimir Prelog (1906-1998,1975NP HO 卡茄碱Chaconine 龙葵碱的结构 龙葵碱的主要毒性是胃肠道黏膜的刺激性和腐蚀性，以及中枢麻痹。中毒 时的反应就是胃痛加剧，而且出现恶心、呕吐和呼吸困难，全身虚弱，严重者 就会死亡。龙葵碱对人的致死剂量并不低，但是中毒剂量还是比较低的