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

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

Journal Name: Current Cancer Drug Targets

Volume 15 , Issue 6 , 2015

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Graphical 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.

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

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Article Details

Year: 2015
Page: [504 - 510]
Pages: 7
DOI: 10.2174/1568009615666150506093155
Price: $65

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