Mótyán Gergő, Kádár Zalán, Kovács Dóra, Wölfling János, Frank Éva
Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
Steroids. 2014 Sep;87:76-85. doi: 10.1016/j.steroids.2014.05.019. Epub 2014 Jun 10.
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.
通过芳基腈氧化物与甾体α,β-不饱和酮的1,3-偶极环加成反应，高效合成了含有与A环或D环稠合的异恶唑啉部分的新型5α-雄甾烷。在环化过程中，腈氧化物偶极子的O端连接到亲偶极体β-碳上的区域异构体以立体选择性方式形成，仅提供1α,2α-或15β,16β-稠合杂环。结果表明，六元A环的环状烯酮部分的反应性低于五元D环，但所有反应都受到腈氧化物取代模式的显著影响。根据用于A环稠合杂环的碱的不同，初级产物的17-脱乙酰化导致芳构化或同时羟基化，而在3-脱乙酰化过程中，D环稠合类似物部分或完全观察到类似逆迪克曼的碎片化。
