去甲斑蝥素类化合物、合成及其抗癌活性：新型去甲斑蝥素类似物的合成及其抗癌活性评估
Norcantharimides, synthesis and anticancer activity: Synthesis of new norcantharidin analogues and their anticancer evaluation.
作者信息
Hill Timothy A, Stewart Scott G, Ackland Stephen P, Gilbert Jayne, Sauer Benjamin, Sakoff Jennette A, McCluskey Adam
机构信息
Chemistry, Chemistry Building, The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia.
出版信息
Bioorg Med Chem. 2007 Sep 15;15(18):6126-34. doi: 10.1016/j.bmc.2007.06.034. Epub 2007 Jun 20.
A range of amines was reacted with norcantharidin (2) to provide the corresponding norcantharimides (9-43). Treatment of norcantharidin with allylamine afforded the corresponding allyl-norcantharimide (20) which was amenable to epoxidation (mCPBA, 22) and subsequent ring opening (MeOH/H(+); 23) or alternatively, osmylation (OsO(4)/NMO; 24). These simple synthetic modifications of 2 facilitated the development of a novel series of norcantharimides displaying modest to good broad spectrum cytotoxicity against HT29 and SW480 (colorectal carcinoma); MCF-7 (breast adenocarcinoma); A2780 (ovarian carcinoma); H460 (lung carcinoma); A431 (epidermoid carcinoma); DU145 (prostate carcinoma); BE2-C (neuroblastoma); and SJ-G2 (glioblastoma). Analogues possessing a C(10), C(12) or C(14) alkyl chain or a C(12) linked bis-norcantharimide displayed the highest levels of cytotoxicity.
一系列胺类化合物与去甲斑蝥素（2）反应，得到相应的去甲斑蝥酰亚胺（9 - 43）。用烯丙胺处理去甲斑蝥素得到相应的烯丙基 - 去甲斑蝥酰亚胺（20），该化合物可进行环氧化反应（间氯过氧苯甲酸，22）及随后的开环反应（甲醇/氢离子；23），或者进行锇氧化反应（四氧化锇/ N - 甲基氧化吗啉；24）。对2进行的这些简单合成修饰促进了一系列新型去甲斑蝥酰亚胺的开发，这些化合物对HT29和SW480（结肠直肠癌）、MCF - 7（乳腺腺癌）、A2780（卵巢癌）、H460（肺癌）、A431（表皮样癌）、DU145（前列腺癌）、BE2 - C（神经母细胞瘤）和SJ - G2（胶质母细胞瘤）显示出中等至良好的广谱细胞毒性。具有C(10)、C(12)或C(14)烷基链或C(12)连接的双去甲斑蝥酰亚胺的类似物表现出最高水平的细胞毒性。
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