The facile synthesis of the 5Z,9Z-dienoic acids and their topoisomerase I inhibitory activity.
An original, effective approach to the synthesis of natural and synthetic 5Z,9Z-dienoic acids in high yields (61-67%) and with high selectivity (>98%) was developed. The approach is based on the use of the new intermolecular catalytic cross cyclomagnesiation of terminal aliphatic and oxygenated 1,2-dienes upon treatment with Grignard reagents in the presence of the Cp2TiCl2 catalyst. High activity of (5Z,9Z)-5,9-eicosadienoic acid as a human topoisomerase I inhibitor at concentrations above 0.1 μM was elucidated.
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, 450075, Ufa, Russian Federation. DyakonovVA@gmail.com.
Vladimir A
VA
D'yakonov
Aleksey A
AA
Makarov
Lilya U
LU
Dzhemileva
Elina Kh
EKh
Makarova
Elza K
EK
Khusnutdinova
Usein M
UM
Dzhemilev
D000466:Alkadienes / Q000737:chemistry; D002384:Catalysis; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
C404169:5,9-eicosadienoic acid; D000466:Alkadienes; D005231:Fatty Acids, Unsaturated; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I