4－（取代氨基酸酰胺基）－4－脱氧－4′－去甲基表鬼臼毒素的合成及其抗肿瘤活性

Synthesis and Antitumor Activity of 4-[(2S)Carbobenzyloxyaminoacyl]Amino-4-Deoxy-4′-Demethylepipodophyllotoxins

合成了１８个Ｎ－苄氧羰基保护的４－取代氨基酸酰胺基－４－脱氧－４′－去甲基表鬼臼毒素衍生物。它们在体外试验中显示出良好的抗Ｌ１２１０白血病细胞（ＩＣ５０２．７×１０－１～４．０×１０－４ｍｇ／Ｌ）和ＫＢ细胞的活性，部分新化合物的抗Ｌ１２１０和ＫＢ细胞的活性超过依托泊甙［Ｅｔｏｐｏｓｉｄｅ，ＩＣ５０（Ｌ１２１０）１．０×１０－１ｍｇ／Ｌ］。

Eighteen 4-[(2S)-Carbobenzyloxyaminoacyl] amino-4-deoxy-4′-demethylepipodophyllo-toxins were synthesized by condensation of 4-amino-4-deoxy-4′-demethylepipodophyl-lotoxin and N-carbobenzoxy-amino acid, such as lycin, L-alanine, L-phenylalanine, L-serine, L-lysine, L-tryptophan, DL-methionine, L-leucine, L-isoleucine etc,in the presenec of diethyl cyanophosphonate and triethylamine in DMF. In the in vitro test,all title compounds exhibited remarkable antitumor activity against L1210 and KB cell lines(IC501. 8×10-1～4. 0×10-4mg/L, L1210). Some of them showed more potent activity than that of etoposide.