Tsujimoto Mitsuhiro, Lowtangkitcharoen Witaya, Mori Nanae, Pangkruang Waree, Putongking Ploenthip, Suwanborirux Khanit, Saito Naoki
Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University.
Chem Pharm Bull (Tokyo). 2013;61(10):1052-64. doi: 10.1248/cpb.c13-00525.
We report herein eleven 2'-N-acyl derivatives that were prepared from ecteinascidin 770 (Et 770: 1b) via 18,6'-O-bisallyl protected compound (4) in excellent yields. 2'-N-Acyl derivatives (6a-k) generally showed higher cytotoxicity than 1b. Among them, 3-quinolineacyl derivative (6g) and 4-fluorocinnamoyl derivative (6h) exhibited approximately 50- and 70-fold higher cytotoxicity to the HCT116 human colon carcinoma cell line, respectively, than 1b. Both compounds are potent inhibitors of the in vitro growth of several tumor cells and are therefore promising leads for further optimization. We also report the transformation of 1b into Et 788 (3), which is the first example of an ecteinascidin derivative having a primary amide at C-21 position.
我们在此报告了11种2'-N-酰基衍生物，它们是由埃博霉素770（Et 770：1b）通过18,6'-O-双烯丙基保护的化合物（4）以优异的产率制备而成。2'-N-酰基衍生物（6a-k）通常显示出比1b更高的细胞毒性。其中，3-喹啉酰基衍生物（6g）和4-氟肉桂酰基衍生物（6h）对HCT116人结肠癌细胞系的细胞毒性分别比1b高约50倍和70倍。这两种化合物都是几种肿瘤细胞体外生长的有效抑制剂，因此是进一步优化的有前景的先导化合物。我们还报告了将1b转化为Et 788（3）的过程，这是在C-21位具有伯酰胺的埃博霉素衍生物的首个实例。
