斑蝥胺素衍生物的合成與細胞毒性之探討

斑蝥胺素衍生物的合成與細胞毒性之探討

 斑蝥為翹翅目芫青科斑芫青屬的昆蟲，主要成分為斑蝥素 (Cantharidin; exo,exo-2,3-Dimethyl- 7-oxabicyclo [2,2,1] hept ane-2,3-dicarboxylic anhydride) ，研究中指出斑蝥素具有發 泡、抗腫瘤的作用，或當作除草劑、殺蟲劑、毛髮生長刺 激劑，目前臨床上則用於治療原發性肝癌及傳染性疣。本 研究合成兩系列之斑蝥胺素衍生物，一方面以斑蝥素與烷 基雙胺為原料，在鹼性環境下高溫封管反應兩小時，冷卻 至室溫後進行脫水反應，經由薄層層析法及再結晶可得到 一系列斑蝥胺素雙體衍生物，另一方面以斑蝥胺素為起始 物，與活化之氮丙啶合成衍生物。此外亦有使用醯亞胺類 與活性之氮丙啶反應，得到一系列衍生物，再經由核磁共 振儀、紅外光光譜儀、高解析度質譜儀確定結構，並進行 細胞毒性試驗。

 Mylabris phalerata, Meloidae family of Coleoptera, has been k nown since antiquity to produce a potent toxic defensive agent, known as cantharidin (exo,exo-2,3-dimethyl-7-oxabicyclo [2.2.

1] heptane-2,3- dicarboxylic anhydride), but well-known as Sp anish Fly. In the past, Cantharidin has used as anticancer, herbi cidal, pesticide and treatment of hepatic carcinoma and mollusc um contagiosum activities.We used cantharidin and serious of diaminoalkane as starting materials, by heating 200 in sealed ℃ tube to form various cantharidinimide dimer. The other hand, we utilized various N-activated aziridine derivatives as starting materials, reacted with cantharidinimide and different imide an alogous to obtain serial derivatives. All of the products were m easured by 1H-NMR, IR, High-resolution mass spectrometry. I n addition, we evaluated these compounds in cytotoxicity

Synthesis and Cytotoxicity of Cantharidinimide Dimers and Imide Analogues