Cytotoxic Lignans from Fruits of Cleistanthus indochinensis: Synthesis of Cleistantoxin Derivatives

Two new aryl-tetralin lignans, 1 and 2, were isolated from the fruits of Cleistanthus indochinensis by bioassay-guided purification. Their structures were determined by spectroscopic analysis including MS and 2D NMR The absolute configurations of 1 and 2 were established from examination of their CD spectra. Compound 1 was cytotoxic against KB cells with an IC50 value of 0.022 mu M, while compound 2 had weaker cytotoxicity, with an IC50 value of 1.4 mu M. When tested against other cancer cell lines (MCF-7, MCF-7R, and HT29), 1 showed an IC50 of 0.014 against MCF-7R cells and an IC50 of 0.036 mu M against MCF-7 cells. A series of amide derivatives of a new lactone, homoderivatives of 1, were prepared. Of these derivatives, only compound 3 had weak cytotoxicity against KB cells.