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

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.

authors

D'yakonov VA,Dzhemileva LU,Makarov AA,Mulyukova AR,Baevd DS,Khusnutdinova EK,Tolstikova TG,Dzhemilev UM

doi

10.2174/1568009615666150506093155

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

504-10

issue

6

eissn

1568-0096

issn

1873-5576

pii

CCDT-EPUB-67089

journal_volume

15

pub_type

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