Synthesis And Antitumor Activity Of 7-(p-fluoro) Benzoyl-camptothecin And Its Derivatives

Camptothecin(CPT),a pentacyclic alkaloid isolated from Chinese tree Camptoth-eca acuminate by ME Wall and MC Wani in1966.It exhibits antitumor activity tomany solid tumors such as gastric carcinoma,lung cancer,hepatoma,rectalcarcinoma,colonic carcinoma and ovarian carcinoma and so on. CPT acts by bindingto the cleavable complex of topoisomerase I-DNA, leading to an accumulation oftriplex complex. The cleavable complex is steadied and the road blocker is formed. Sothe replication fork can't carry through. The replication of DNA is inhibited to causecell death. We synthesized a series of derivatives of camptothecin according to theresearch on the structure activity relation(SAR) of camptotheein. Their cytotoxicitiesof the compounds were tested by SRB assay.A 7-substituted CPT was synthesized starting from CPT. And several20-O-esters of 7-substituted CPT were synthesized.Five new compounds were synthesized in this paper have not been reported. Thestructures of these compounds were conformed by IR,~1H-NMR and elementalanalysis.