Peumusolide A, unprecedented NES non-antagonistic inhibitor for nuclear export of MEK

作者：Tamura Satoru; Hattori Yuuhi; Kaneko Masafumi; Shimizu Nobuhiro; Tanimura Susumu; Kohno Michiaki; Murakami Nobutoshi^*

来源：Tetrahedron Letters, 2010, 51(13): 1678-1681.

DOI：10.1016/j.tetlet.2010.01.068

A new polyketide peumusolide A was disclosed as all unprecedented NES non-antagonistic inhibitor for nuclear export of MEK, a promising scaffold for antitumor agents with novel mechanism of action, from Peumus boldus Molina. The absolute stereostructure as well as optical purity was established by use of the two synthesized enantiomeric model lactones. In addition, the Delta epsilon values in their CD spectra were demonstrated to be the conclusive index for determination of not only configuration at C-3 but also optical purity of natural congeneric polyketides. Peumusolide A was revealed to show NES non-antagonistic action by the biotinylated probe and to inhibit proliferation of MEK-activated tumor cells selectively.

• 出版日期2010-3-31