20(S)-7-乙酰基喜树碱的合成方法改进及其抗肿瘤活性

A New Method of Preparing 20(S)-7-acetylcamptotheicn and Its Antitumor Activity

用硫酸作溶剂,改用过硫酸铵和硫酸亚铁作自由基引发剂,20(S)-7-乙酰基喜树碱收率从36%提高到81.3%。改用丙酮酸代替乙醛,用过硫酸铵和硝酸银作自由基引发剂,20(S)-7-乙酰基喜树碱收率为84%,反应时间仅为4 h。目标产物用SRB法对人白血病细胞(HL-60)、人胃癌细胞(BGC-823)、人肝癌细胞(Bel-7402)和人鼻咽癌细胞(KB)进行了体外抗肿瘤活性试验,研究结果显示,对人肝癌细胞(Bel-7402)和人鼻咽癌细胞(KB)抑制作用很小,对人白血病HL-60和人胃癌BGC-823均有较强抑制作用。

Two new methods of preparing 20（S）-7-acetylcamptotheicn were presented：using sulfuric acid as solvent,ammonium persulfate and iron sulfate heptahydrate as free radical initiators,thus raised the yield of the 20（S）-7-acetylcamptotheicn from 36% to 81.3%.And using pyruvic acid takes the place of acetaldehyde,ammonium persulfate and silver nitrate as free radical initiators,yield of 20（S）-7-acetylcamptotheicn raised to 84% and reaction time reduced to 4 h.The in vitro antitumor activities of the target compound was evaluated by Sulforhodamine B （SRB） assays in four human tumor cell lines, including HL - 60, BGC - 803, Bel - 7402 and KB. The test shows it is weak inhibtion to BGC -803 and KB, but strong inhibtion to HL- 60 and BGC -823.