斑蝥胺素衍生物合成之研究

1. 斑蝥胺素衍生物合成之研究 • 斑蝥胺素衍生物合成之研究斑蝥素 (Cantharidin; exo, exo-2,3-dimethyl-7-oxabicyclo[2.2.1]heptane-2,3-dicarboxlicacid anhydride) ，為翹翅目、莞青科、斑莞青屬的昆蟲於抵禦外侮時所分泌的化合物，具 有顯著的生物活性如引泡發赤、抗腫瘤、刺激毛髮及除草劑等作用。最近曾有研究指出斑蝥素之N-衍生物類斑蝥胺具有一定的抗腫瘤效果且副作用較低。基於減少其毒性增加療效 的目的，本研究進行cantharidin之化學修飾，合成系列之N-衍生物，以便將來進一步作生 物活性評估。經由cantharidin與含氨之取代物於高溫 (約200℃) 含鹼的條件下封管加溫2 小時，餾去溶媒純化後得到四種系列之斑蝥胺素N-衍生物 (aminopyridin和 arylethylamine，aniline 及aminothiazole 系列)，另外，藉由Mitsunobu Reaction將反應物按 一定比例在室溫下反應，使cantharidinimide上之NH官能基與alcohol結合成另一系列斑蝥 素之N-衍生物。已合成的化合物: 斑蝥素之N-衍生物，已由核磁共振儀、 紅外線光譜儀、質譜儀和元素分析儀確定結構。

2. Study on the Synthesis of Cantharidinimide • Cantharidin (exo, exo-2,3-dimethyl-7-oxabicyclo [2.2.1]heptane-2,3-dicarboxlic acid anhydride), isproduced by beetles, belonging to the Order of Coleotera, andFamily of Melodae, as a defense against predators. It hasremarkable biological activity, and can be used as anacantholytic and an antitumor agent, a hair-growth stimulatorand a pesticide. It has been shown inanimal studies that N-derivatives of canthardin have certaininhibitory action on tumors with less side effects. Inorder to further study the activity and toxicity ofrelatedcompounds, we synthesized four series of cantharidinimideby the following method: Cantharidin and amino-containing substrate were heated to 200℃in a sealed tube fortwo hours. After cooling, the residuels were removed fromthe tube, and were further evaporated and purified. Anotherseries of N-cantharidinimide was synthesized by Mitsunobureaction at room temperature. All ofthese cantharidinimide derivatives were tested by 1H-NMR, IR,Mass and Elemental Analysis, and gave consistentspectral data.