中文摘要：

考布他汀-A4（Combretastatins—A4，CA-4）是从天然产物中分离得到的抗癌活性化合物，其分子中Z-构型烯键易异构化转变为无抗癌活性的E．构型．以吡咯-2，5-二酮或吡咯-2-酮代替烯键，设计合成了4个新的CA-4类似物．它们的合成是以3,4-二甲氧基苯乙酮或3-氟-4．甲氧基苯乙酮为起始原料，经d-溴化、改良的Gabriel合成法、与3,4，5-三甲氧基苯乙酸缩合、环化-氧化或环化四步反应完成．其结构用1HNMR，13CNMR，ESI—MS及元素分析进行了表征．用MTT法测试了CA-4类似物对人白血病细胞HL-60、肝癌细胞SMMC-7721和肺腺癌细胞A549的体外抗肿瘤活性．初步结果表明，含氟化合物3,4-二芳基-2，5-吡咯酮（1b）的抗肿瘤活性接近CA-4，IC50值达到0．03～0．05μmol·L-1

英文摘要：

Combretastatins-A4 （CA-4） is a natural product with extraordinary anticancer activity, which was isolated from the South African Tree-Combretum caffrum. However, the~＇ cis-isomer exhibits strong antitubulin activity only, but the cis-isomer tends to isomerize the inactive trans-isomer. In this paper, an additional pyrrolidone ring system was used to replace the cis double bond to arrest the cis-conformation. Thus, four new compounds of 3,4-diaryl pyrrolediones and 3,4-diaryl pyrrolones as CA-4 analogues were synthesized from the starting materials 3,4-dimethoxyacetophenone or 3-fluoro-4-methoxy acetophe- none, via a four steps reaction, a-bromination, improved Gabriel reaction, condensation with 3,4,5-trimethoxyphenylacetic acid and intramolecular cyclization under air or nitrogen. The structures of these new compounds were confirmed by 1H NMR, 13C NMR, ESI-MS and elemental analysis. The in vitro antitumor activities of CA-4 analogues against HL-60, SMMC-7721 and A549 human gastric cancer cell lines were tested using colorimetric MTT assay. The preliminary result indicates that 3-（3-fluoro-4-methoxyphenyl）-4-（3,4,5-trimethoxyphenyl）pyrrole-2,5-dione （lb） shows significant antitumor activity （0.03- 0.05 μmol.L-1）, which is closely to the natural CA-4,