11-Phenylundeca-5Z,9Z-dienoic Acid: Stereoselective Synthesis and Dual Topoisomerase I/IIα Inhibition

(5Z,9Z)-11-Phenylundeca-5,9-dienoic acid was stereoselectively synthesized, based on original cross-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy) tetrahydro-2H-pyran and buta-2,3-dien-1-ylbenzene with EtMgBr in the presence of the Cp2TiCl2 catalyst giving 2,5-dialkylydenemagnesacyclopentane in 86% yield. The acid hydrolysis of the product and Jones oxidation of the resulting 2-{[(5Z, 9Z)-11-phenylundeca-5,9-dien-1-yl]oxy}tetrahydro-2H-pyran afforded (5Z, 9Z)-11-phenylundeca-5,9-dienoic acid in an overall yield of 75%. A high inhibitory activity of the synthesized acid with respect to human topoisomerase I (hTop1) and II (hTop2 alpha) was detected. Resorting to the data of molecular docking, a mechanism of inhibition was proposed.