新型3-五元碳环螺环氧化吲哚类化合物的合成及其抗人白血病细胞活性

以氧化吲哚与邻芳基二甲醛为原料,经Knoevenagel缩合(或Michael,环化反应),制得7个3-五元碳环螺环氧化吲哚(4a~4c,产率67%~86%,d/r值4∶1~10∶1)和4d~4g;4d~4g与哌啶(或四氢吡咯)和多聚甲醛经胺甲基化反应,合成了4个3-五元碳环螺环氧化吲哚(5d~5g),产率55%~67%,d/r值10∶1~20∶1,其结构经~1H NMR,~(13)C NMR和HR-MS(ESI-TOF)表征。采用MTT法研究了4a~4c和5d~5g对人白血病细胞(K562)的体外抗肿瘤活性。结果表明:4b,5d和5f对K562抑制活性较好,IC50分别为29.3μmol·L~(-1),27.4μmol·L~(-1)和34.2μmol·L~(-1),与阳性对照药顺铂(26.8μmol·L~(-1))相当。

Synthesis of Novel Five-membered Carbocyclic Spirooxindoles and Their Activities Against Human Leukemia Cells

Seven novel five-membered carbocyclic spirooxindoles(4a~4c and 4d~4g) were prepared by knoevenagel condensation( or Michael, cyclization) , using oxindole and o-aryldicarboxaldehyde as the materials. The yields and d/r of 4a~4c were 67% ~86% and 4 :1~10 :1, respectively. Four five-membered carbocyclic spirooxindoles(5d~5g) were synthesized by the aminomethylation reaction of 4d~4g with piperidine(or pyrrdidine) and paraformaldehyde. The yields and d/r of 5d~5g were 55% ~67% and 10 :1 ~ >20 :1, respectively. The structures were characterized by 1 H NMR, 13 C NMR and HR-MS ( ESI-TOF ) . The in vitro antitumor activities against human leukemia cells (K562) were demonstrated by MTT assays. The results showed that 4b, 5d and 5f showed best activi-ties equipotent than the positive control of Cisplatin(26. 8 μmol·L-1), with IC50 of 29. 3 μmol·L-1 , 27. 4 μmol·L-1 and 34. 2 μmol·L-1 , respectively.