Catalytic cyclometallation in steroid chemistry III: Synthesis of steroidal derivatives of 5Z,9Z-dienoic acid and investigation of its human topoisomerase I inhibitory activity.
Two approaches to stereoselective synthesis of steroid 5Z,9Z-dienoic acids were developed, the first one being based on the cross-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran and 1,2-diene cholesterol derivatives on treatment with EtMgBr catalyzed by Cp2TiCl2, while the other involving the synthesis of esters of hydroxy steroids with (5Z,9Z)-tetradeca-5,9-dienedioic acid, prepared in two steps using homo-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran as the key step. High inhibitory activity of the synthesized acids against human topoisomerase I (hTop1) was found.
Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075 Ufa, Russian Federation. Electronic address: DyakonovVA@gmail.com.
Vladimir A
VA
D'yakonov
Department of Immunology and Human Reproductive Health, Bashkir State Medical University, 3 Lenin Street, Ufa, Bashkortostan 450003, Russian Federation. Electronic address: Dzhemilev@mail.ru.
Lilya U
LU
Dzhemileva
Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075 Ufa, Russian Federation.
Regina A
RA
Tuktarova
Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075 Ufa, Russian Federation.
Aleksey A
AA
Makarov
Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075 Ufa, Russian Federation.
Ilgiz I
II
Islamov
Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075 Ufa, Russian Federation.
Alfiya R
AR
Mulyukova
Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt Oktyabrya, 450075 Ufa, Russian Federation.
Usein M
UM
Dzhemilev
D004264:DNA Topoisomerases, Type I / Q000737:chemistry*; D006801:Humans; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry
D013256:Steroids; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I
5Z,9Z-dienoic acids; Cross-cyclomagnesiation; Dzhemilev reaction; Grignard reagents; Magnesacyclopentane; Titanocene dichloride; Topoisomerase I inhibitors