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对4’-去甲表鬼臼毒素的C_4位进行化学修饰,合成和筛选了10个4-烷硫基-4-脱氧-4’-去甲表鬼臼毒素衍生物以进一步研究C_4位不同的原子和取代基与活性之间的关系及寻找结构简单、活性更强的抗肿瘤新药。4’-去甲表鬼臼毒素与硫醇在三氟化硼·乙醚或三氟乙酸存在下生成相应的硫醚,也可用硫醇与4β-溴-4-脱氧-4’-去甲表鬼臼毒素反应生成相应的硫醚。在体外筛选中,化合物10和12抑制L1210白血病细胞的活性与依托泊甙相当或更强,化合物9,10,12和15抑制KB细胞的活性与依托泊甙相当或更强。
The C_4 position of 4’-demethylepipodophyllotoxin was chemically modified and 10 4-alkylthio-4-deoxy-4’-demethylepipodophyllotoxin derivatives were synthesized and screened for further study of C_4 position differences Of the relationship between atoms and substituents and activity and to find a simple structure, more active anti-tumor drugs. 4’-nor-epipodophyllotoxin with thiols in the presence of boron trifluoride diethyl ether or trifluoroacetic acid to form the corresponding thioethers can also be used with thiols and 4β-bromo-4-deoxy-4’- Podophyllotoxin reacts to form the corresponding thioether. Compounds 10 and 12 inhibited the activity of L1210 leukemia cells comparable to or more potent than etoposide in in vitro screens. Compounds 9, 10, 12 and 15 inhibited the activity of KB cells comparable to or greater than that of etoposide.