Synthesis of novel steroidal 16-spiroisoxazolines by 1,3-dipolar cycloaddition, and an evaluation of their antiproliferative activities in vitro.
Mol Divers
; 18(3): 521-34, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24691697
ABSTRACT
Efficient synthesis of novel 16-spiroisoxazolines in the androst-5-ene series was carried out by 1,3-dipolar cycloadditions of different aryl nitrile oxides to 3ß-acetoxy-16-methylene-androst-5-en-17-one. During the intermolecular ring closures, the attack of the O terminus of the nitrile oxide dipole from the α side on C-16 predominated for steric reasons permitting the reactions to occur in a regio- and stereoselective manner. The minor isomers in which the angular methyl group on C-13 and the O atom of the isoxazoline heteroring were in the ß, ß-cis orientation were obtained in a yield of only ~10 %. Moreover, the conversions were influenced to a certain extent by the substituents on the aromatic moiety of the 1,3-dipoles. The stereostructures of the related diastereomers were confirmed by 2D NMR methods. Deacetylation of the primarily formed main products resulted in the corresponding 3ß-OH analogs, which were further reduced to furnish 3ß, 17ß-diols. All of the synthetized compounds were subjected to in vitro pharmacological studies in order to investigate their antiproliferative effects on three malignant human adherent cell lines (HeLa, MCF7, and A431).
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Base de dados:
MEDLINE
Assunto principal:
Compostos de Espiro
/
Reação de Cicloadição
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Isoxazóis
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article