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

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

Volume: 15 Issue: 6

Author(s): Vladimir A. D’yakonov, Lilya U. Dzhemileva, Aleksey A. Makarov, Alfiya R. Mulyukova, Dmitry S. Baevd, Elza K. Khusnutdinova, Tatiana G. Tolstikova and Usein M. Dzhemilev

Affiliation:

Keywords: Cyclomagnesiation, docking, fatty acids, homogeneous catalysis, novel topoisomerase I and IIα inhibitors, stereoselective synthesis of 5Z, 9Z-dienoic acid.

Abstract: (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-2Н-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 (hTop2α) was detected. Resorting to the data of molecular docking, a mechanism of inhibition was proposed.

Cite this article as:

D’yakonov Vladimir A., Dzhemileva Lilya U., Makarov Aleksey A., Mulyukova Alfiya R., S. Baevd Dmitry, Khusnutdinova Elza K., Tolstikova Tatiana G. and Dzhemilev Usein M., 11-Phenylundeca-5Z,9Z-dienoic Acid: Stereoselective Synthesis and Dual Topoisomerase I/IIα Inhibition , Current Cancer Drug Targets 2015; 15 (6) . https://dx.doi.org/10.2174/1568009615666150506093155