Synthesis of antiproliferative 13α-d-homoestrones via Lewis acid-promoted one-pot Prins–Ritter reactions of d-secosteroidal δ-alkenyl-aldehydes

Abstract A simple one-pot Prins–Ritter route was developed for the synthesis of 16-acylamino-17a-hydroxy-d-homoestrone 3-benzyl and 3-methyl ethers in the 13α-estrone series. The d-secosteroidal δ-alkenyl-aldehydes were allowed to react with different nitriles in the presence of BF3·OEt2 as a Lewis...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Huber Judit
Wölfling János
Schneider Gyula
Ocsovszki Imre
Varga Mónika
Zupkó István
Mernyák Erzsébet
Dokumentumtípus: Cikk
Megjelent: 2015
Sorozat:STEROIDS 102
doi:10.1016/j.steroids.2015.07.004

mtmt:2932883
Online Access:http://publicatio.bibl.u-szeged.hu/6934
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520 3 |a Abstract A simple one-pot Prins–Ritter route was developed for the synthesis of 16-acylamino-17a-hydroxy-d-homoestrone 3-benzyl and 3-methyl ethers in the 13α-estrone series. The d-secosteroidal δ-alkenyl-aldehydes were allowed to react with different nitriles in the presence of BF3·OEt2 as a Lewis acid catalyst. Prins cyclizations afforded 17a-hydroxy-16-carbenium ions, which underwent Ritter reactions with nitriles, leading to 16α- or 16β-acylamino derivatives. A side-product in which a dihydro-1,3-oxazine was bridged to six-membered ring D at positions 16α,17aα was formed in each reaction. The antiproliferative properties of the novel 13α-d-homosteroids were determined on a panel of human adherent cancer cell lines (HeLa, MCF-7, T47D, MDA-MB-231, MDA-MB-361, A2780 and A431) by means of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays. Some compounds proved to be more effective (with submicromolar IC50 values) than the reference agent cisplatin. One of the most potent compounds substantially increased the rate of tubulin polymerization. Cell cycle analyses by flow cytometry indicated a concentration-dependent accumulation of the G2/M cell population. 
700 0 1 |a Wölfling János  |e aut 
700 0 1 |a Schneider Gyula  |e aut 
700 0 1 |a Ocsovszki Imre  |e aut 
700 0 1 |a Varga Mónika  |e aut 
700 0 1 |a Zupkó István  |e aut 
700 0 1 |a Mernyák Erzsébet  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/6934/1/143_Steroids_2015.pdf  |z Dokumentum-elérés