斑蝥胺素衍生物合成之研究
Study on the Synthesis of Cantharidinimide
中文摘要
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。
英文摘要
Cantharidin (exo, exo-2,3-dimethyl-7-oxabicyclo [2.2.1]
heptane-2,3-dicarboxlic acid anhydride), is
produced by beetles, belonging to the Order of Coleotera, and Family of Melodae, as a defense against predators. It has remarkable biological activity, and can be used as an
acantholytic and an antitumor agent, a hair-growth stimulator and a pesticide. It has been shown in
animal studies that N-derivatives of canthardin have certain inhibitory action on tumors with less side effects. In
order to further study the activity and toxicity of
relatedcompounds, we synthesized four series of cantharidinimide by the following method: Cantharidin and amino-
containing substrate were heated to 200℃in a sealed tube for two hours. After cooling, the residuels were removed from the tube, and were further evaporated and purified. Another
series of N-cantharidinimide was synthesized by Mitsunobu reaction at room temperature. All of
these cantharidinimide derivatives were tested by 1H-NMR, IR, Mass and Elemental Analysis, and gave consistent
spectral data.
