Ilgiz I. Islamov

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.

Synthesis and transformations of metallacycles. 45. Cross-cyclomagnesiation of 1,2-dienes in the synthesis of 5Z,9Z-dienoic acids, efficient inhibitors of human topoisomerase I

An original method for the synthesis of natural and synthetic 5Z,9Z-dienoic acids with high selectivity (>98%) and ~50% yields was elaborated. The method is based on a new Cp2TiCl2catalyzed cross-cyclomagnesiation reaction of terminal aliphatic and O-containing 1,2-dienes using Grignard reagents. The synthesized acids exhibited in vitro high inhibiting activity against human topoisomerase I.

Synthesis and transformations of metallacycles 42. Cp2ZrCl2-Catalyzed cycloalumination of 3-methylidenespiro[cyclobutane-1,3′-(5′α)-cholestane] with Et3Al

A Cp2ZrCl2-catalyzed cycloalumination of 3-methylidenespiro[cyclobutane-1,3′-(5′α)-cholestane] with Et3Al gives 3-ethyl-3-aluminadispiro[cyclopentane-1,1′-cyclobutane-3′,3″-(5″α)-cholestane] in 84% yield.

Synthesis and transformations of metallacycles 44. Cycloalumination of methylenecyclobutane terpene derivatives with Et3Al catalyzed by Cp2ZrCl2

Cycloalumination of methylenecyclobutane terpene derivatives (d(+)-camphor, (+)-camphene, β-pinene, and l(–)-menthol) with Et3Al catalyzed by Cp2ZrCl2 produced novel spirofused organoaluminum compounds in high yields. The synthesized compounds were in situ transformed into the corresponding spiro tetrahydroselenophenes and spiro phospholanes.

Catalytic cyclometallation in steroid chemistry IV: Efficient method for the synthesis of tetrahydrothiophene, tetrahydroselenophen and cyclopentanone derivatives of (5α)-cholestane

Catalytic cycloalumination of (3β,5α)-3-vinylcholestane and (3α,5α)-3-allylcholestane with Et3Al catalyzed by Cp2ZrCl2 was performed for the first time to give previously unknown aluminacyclopentanes in ∼90% yield; these products were converted in situ to carbo- and heterocyclic (5α)-cholestane derivatives.