EDCI/DMAP存在下7-乙基喜树碱与乙酰水杨酸的反应

摘要

以EDCI为脱水剂,DMAP为催化剂,对7-乙基喜树碱与乙酰水杨酸的酯化反应进行了研究。经硅胶柱层析纯化和波谱结构鉴定,所得产物并非预期的酯化产物———20(S)-O-乙酰水杨酸-7-乙基喜树碱酯(2),而是20(S)-O-乙酸-7-乙基喜树碱酯(3)。推测在此条件下7-乙基喜树碱优先与乙酰水杨酸的酯基之间发生了酯交换反应,通过反应机理对上述反应结果进行了解释。化合物3在8 mg·kg-1剂量腹腔给药,对小鼠肉瘤S180较弱抑瘤活性。%The esterification reaction of acetylsalicylic acid and 7-ethylcamptothecin in presence of EDCI/DMAP was investigated. The product was purified by silica gel column chromatography and the structure was identified by IR,1 HNMR and HR-MS. The product was not expected 7-ethylcamptothecin acetylsalicylate(2)but 7-ethylcamptothecin acetate(3). It was speculated that ester exchange reaction between hydroxy group of 7-ethylcamptothecin and ester group of acetylsalicylic acid was preferentially occurred under the reaction condition. The reaction result might be explained by an ester exchange reaction mechanism. Compound 3(i. p. 8 mg·kg-1 ) had weak antitumor effect on S180 mice model.