Regio- and stereoselective access to novel ring-condensed steroidal isoxazolines

• Published in: Steroids Vol. 87; pp. 76 - 85
• Main Authors: Mótyán, Gergő, Kádár, Zalán, Kovács, Dóra, Wölfling, János, Frank, Éva
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2014
• Subjects: 5α-Androstanes; Cycloaddition; Cycloaddition Reaction; Isoxazoles - chemical synthesis; Isoxazoles - chemistry; Isoxazolines; Regioselectivity; Stereocontrol; Stereoisomerism; Steroids - chemistry; Substrate Specificity; Cycloaddition; Isoxazolines; Regioselectivity; 5α-Androstanes; Stereocontrol
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2014.05.019

•Isoxazoline hetero rings were introduced into the sterane nucleus.•Intermolecular alkene–nitrile oxide cycloadditions were carried out.•The reactivities of the enone moiety of rings A and D were compared.•Behaviour of the synthetized compounds under deacetylation was studied.•The structures of all novel compounds were confirmed by NMR measurements.
Novel 5α-androstanes containing an isoxazoline moiety condensed to ring A or D were efficiently synthetized by 1,3-dipolar cycloadditions of aryl nitrile oxides to steroidal α,β-unsaturated ketones. During the ring closures, regioisomers in which the O terminus of the nitrile oxide dipoles is attached to the β-carbon of the dipolarophile were formed in a stereoselective manner to furnish exclusively 1α,2α- or 15β,16β-condensed heterocycles. The cyclic enone moiety of the six-membered ring A proved to be less reactive than that of the five-membered ring D, but all the reactions were affected significantly by the substitution pattern of the nitrile oxide. 17-Deacetylation of the primary products resulted in aromatization or simultaneous hydroxylation, depending on the base applied for the ring A-fused heterocycles, while retro-Dieckmann-like fragmentation was observed partially or completely for the ring D-fused analogues during 3-deacetylation.