1010433-25-6Relevant articles and documents
Total synthesis and biological evaluation of grassypeptolide A
Liu, Hui,Liu, Yuqing,Wang, Zhuo,Xing, Xiangyou,Maguire, Anita R.,Luesch, Hendrik,Zhang, Hui,Xu, Zhengshuang,Ye, Tao
supporting information, p. 6774 - 6784 (2013/06/27)
Herein, we describe in full our investigations into the synthesis of grassypeptolide A (1) in 17 linear steps with an overall yield of 11.3 %. In particular, this work features the late-stage introduction of sensitive bis(thiazoline) heterocycles and 31-membered macrocyclization conducted at the sterically congested secondary amide site in superb conversion (72 % yield). Biological evaluation indicated that grassypeptolide A significantly inhibited cancer cell proliferation in a dose-dependent manner. It induced cancer cell apoptosis, which was associated with increased cleavage of poly(ADP-ribose) polymerase (PARP) and decreased expression of bcl-2 and bcl-xL. Furthermore, grassypeptolide A also caused cell cycle redistribution by increasing cells in the G1 phase and decreasing cells in the S and G2 phases. In addition, cell cycle arrest was correlated with downregulation of cyclin D and upregulation of p27 and p21. Cytotoxic activity: Synthesis of grassypeptolide A, an anticancer marine cyclodepsipeptide, in 17 linear steps with an overall yield of 11.3 % is described (see figure). Subsequent biological evaluation indicated that grassypeptolide A significantly inhibited cancer-cell proliferation in a dose-dependent manner. Copyright
