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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Regio- and stereoselective access to novel ring-condensed steroidal isoxazolines
Gergő Mótyán1, Zalán Kádár1, Dóra Kovács1
1Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
Abstract:
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.
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