4-酰硫基-4-脱氧-4-去甲表鬼臼毒素衍生物的合成和抗肿瘤活性

为研究4’-去甲表鬼臼毒素的C₄位不同原子及不同取代基类型同活性之间的关系,寻找活性高、毒性低的抗肿瘤新药,合成了11个4-酰硫基-4-脱氧-4’-去甲表鬼臼毒素,衍生物并进行了抗肿瘤活性试验。4-巯基-4-脱氧-4’-去甲表鬼臼毒素和不同的羧酸在二乙氧基磷酰氰酯存在下得相应的硫酯。该类化合物在L1210白血病细胞和KB细胞的体外抑制试验中普遍表现出抑制活性。化合物10的活性与依托泊甙相当。其余活性比依托泊甙差。与相应的C₄位酰氨基的4’-去甲表鬼臼毒素衍生物相比,活性明显弱。提示氮取代的衍生物活性更好。

Synthesis and antitumor activities of 4-acylthiol-4-deoxy-4'-demethylepipodophyllotoxin analogues]

This paper describes the synthesis and antitumor activity of 4-acylthiol-4-deoxy-4'-demethylepipodophyllotoxin analogues. 4-Mercapto-4-deoxy-4'-demethylepipodophyllotoxin prepared from 4'-demethylepipodophyllo-toxin with H2S in the presence of BF3.Et2O, was acylated with different acids using diethyl cyanophosphonate and thus, corresponding 4-acylthiol-4-deoxy-4'-demethyl epipodophyllotoxin analogues were synthesized. These compounds were screened in L1210 leukemia and KB cells, and one compound has activity similar to etoposide, and others were generally weaker than etoposide and corresponding 4-acylamido-4-deoxy-4'-demethylepipodophyllotoxin analogues.