Total Synthesis of Natural Lembehyne C and Investigation of Its Cytotoxic Properties
Lilya U. Dzhemileva, Vladimir A. D’yakonov, А. А. Макаров, E. Kh. Makarova, Evgeny N. Andreev, У. М. Джемилев
Abstract
The first Z-stereoselective method for the synthesis of the natural marine alkynol lembehyne C, containing a 1Z,5Z,9Z-triene moiety, in 41% yield was developed using the new Ti-catalyzed cross-coupling of oxygenated and aliphatic 1,2-dienes as the key step. It was found for the first time that lembehyne C exhibits moderate cytotoxicity against Jurkat, K562, U937, and HL60 cancer cells and also efficiently induces apoptosis in Jurkat cells, with the cell death mechanism being activated by the mitochondrial pathway. The lembehyne C inhibition of the cell cycle follows the mitotic catastrophe mechanism.
Topics & Concepts
Jurkat cellsStereochemistryK562 cellsCytotoxicityMoietyCytotoxic T cellMitosisStereoselectivityApoptosisChemistryBiologyBiochemistryIn vitroCell biologyCatalysisGeneticsT cellImmune systemMarine Sponges and Natural ProductsSynthetic Organic Chemistry MethodsMicrobial Natural Products and Biosynthesis