Efficient approach to novel 1α-triazolyl-5α-androstane derivatives as potent antiproliferative agents

Abstract

Stereoselective 1,4-Michael addition of azoimide to 17β-acetoxy-5α-adrost-1-en-3-one was carried out to furnish a 1α-azido-3-ketone, which was reduced to give the 3β- and 3α-hydroxy epimers in a ratio of 5 : 2. The Cu(I)-catalyzed 1,3-dipolar cycloaddition of the major isomer to terminal alkynes afforded 1α-triazolyl derivatives, which were deacetylated to the corresponding 3β,17β-diols or oxidized to the analogous 3-ketones. However, the ability of the minor 1α,3α-azidoalcohol to undergo similar cyclization was found to be affected significantly by the steric bulk of the substituents on the alkyne reaction partner. All triazolyl compounds were tested in vitro on three malignant gynecological cell lines (HeLa, MCF7 and A2780).

Synthesis of sex hormone-derived modified steroids possessing antiproliferative activity

“…After a systematic study of D-ring-substituted triazolyl compounds, a number of analogous derivatives were prepared in which the triazoles were connected to ring A [81]. Starting from unsaturated ketone 138, an azido group was introduced onto position 1 of the sterane skeleton by Michael addition, which resulted stereoselectively in the 1␣-azido isomer 139 due to the steric bulk of the neighboring angular methyl group.…”

Synthesis of novel steroidal 16-spiroisoxazolines by 1,3-dipolar cycloaddition, and an evaluation of their antiproliferative activities in vitro

“…As a continuation of our work for the construction of heterocyclic steroids possessing cell-growth inhibitory effect [29][30][31][32], we decided to prepare novel 16-spiroisoxazolinyl androst-5-ene derivatives from an α,β-unsaturated steroidal 17-ketone via 1,3-dipolar cycloaddition. Our goal was to investigate the regio-and stereoselectivity of the process and the influence of steric and electronic factors on the ringclosure reactions.…”

Szteránvázhoz kondenzált nitrogéntartalmú heterociklusok szintézise bifunkciós nemi hormon származékokból

“…Applying similar conditions to those used previously in the Vilsmeier-Haack reaction for the synthesis of bifunctional streoid derivative, the transformation of 17β-acetoxy-5α-dihydrotestosterone (10) resulted in an unwanted bis-formylated product (12).…”

“…A csoport egyik kutatási irányvonalát a citosztatikus hatású nemi hormon származékok szintézise képezi. [10][11][12][13][14][15] A szerkezetmódosítások további célja az eredeti hormonális aktivitás csökkentése vagy teljes megszüntetése a nem kívánt és kellemetlen mellékhatások kiküszöbölése érdekében.…”