11-PHENYLUNDECA-5Z,9Z-DIENOIC ACID: STEREOSELECTIVE SYNTHESIS AND DUAL TOPOISOMERASE I/IIΑ INHIBITION

Дьяконов, В.А.; Джемилева, Л.У.; Макаров, А.А.; Мулюкова, А.Р.; Хуснутдинова, Э.К.; Джемилев, У.М.; Толстикова Т. Г.; Baev, D.S.; D`yakonov, V.A.; Dzhemileva, L.U.; Makarov, A.A.; Mulyukova, A.R.; Khusnutdinova, E.K.; Dzhemilev, U.M.; Tolstikova, Tatiana G.

11-PHENYLUNDECA-5Z,9Z-DIENOIC ACID: STEREOSELECTIVE SYNTHESIS AND DUAL TOPOISOMERASE I/IIΑ INHIBITION

Дьяконов, В.А., Джемилева, Л.У., Макаров, А.А., Мулюкова, А.Р., Хуснутдинова, Э.К., Джемилев, У.М., Толстикова Т. Г., Baev, D.S., D`yakonov, V.A., Dzhemileva, L.U., Makarov, A.A., Mulyukova, A.R., Khusnutdinova, E.K., Dzhemilev, U.M., Tolstikova, Tatiana G.

Дата публикации: 2015

Дата публикации в реестре: 2020-10-28T16:06:24Z

Аннотация:

(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.

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

Тип: Article