海洋环肽Phakellistatin13的全合成研究TotalSynthesisofAMarine.PDF

2007 年第65 卷 化 学 学 报 Vol. 65, 2007 第3 期, 253～256 ACTA CHIMICA SINICA No. 3, 253～256 ·研究论文· 海洋环肽 Phakellistatin 13 的全合成研究 蒋庆锋 周有骏* 姚建忠 吕加国 朱 驹 姚 斌 郑灿辉 盛春泉 (第二军医大学药学院药物化学教研室 上海 200433) 摘要 Phakellistatin 13 是从海绵中分离得到的高活性的抗肿瘤环七肽化合物, 是优良的抗肿瘤先导化合物. 我们结合 逐步接肽法和片段缩合法, 首次采用液相法完成 Phakellistatin 13 的全合成, 并提出与以往报道不同的多肽环合策略. 目标化合物经质谱与核磁共振光谱结构确证与天然产物一致, 为进一步开展Phakellistatin 13 及其类似物的抗肿瘤活性 研究打下了扎实的基础. 关键词 Phakellistatin 13; 液相; 全合成; 环肽 Total Synthesis of A Marine Cyclopeptide: Phakellistatin 13 JIANG, Qing-Feng ZHOU, You-Jun* YAO, Jian-Zhong LÜ, Jia-Guo ZHU, Ju YAO, Bin ZHENG, Can-Hui SHENG, Chun-Quan (School of Pharmacy, Second Military Medical University, Shanghai 200433) Abstract Phakellistatin 13 is a cycloheptapeptide isolated from sponge and show good suppression action to human hepatoma BEL-7404 cell line. We synthesized Phakellistatin 13 the first time by solution method combination of stepwise coupling and segment condensation and the final deprotection and cyclization were achieved according to our designed method, which was different from the reported process. Comparison of 1 13 the natural and synthetic specimens of phakellistatin 13 by H and C NMR spectra gave identical NMR signals. The total synthesis of phakellistatin 13 is significant to further study its derivatives and develop novel antitumor drugs. Keywords Phakellistatin 13; cyclopeptide; solution