11-苯十一基-5Z,9Z-二烯酸：立体选择性合成和双拓扑异构酶 I/IIα抑制

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 and Dmitry S. Baevd, Elza K. Khusnutdinova, Tatiana G. Tolstikova and Usein M. Dzhemilev

Affiliation:

关键词: 环镁化，对接，脂肪酸，均相催化，新的拓扑异构酶I和IIα抑制剂，立体选择性合成

摘要: (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:

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