Synthesis of [1,2,4]-triazolo-annulated 3-aza-A-homocholestanes—A novel class of pentacyclic compounds

This study was performed to investigate the reactivity of azocarbenium salts derived from 5α-cholestan-3-one towards 1,3-dipolar cycloaddition reactions with inverse electron-demand to produce unprecedented steroidal heterocyclic derivatives, i.e. [1,2,4]-triazolo-annulated 3-aza-A-homocholestanes 8 and 11 and picrates 12. The synthetic steps were comprised of oxidizing hydrazones 3 with tert-butyl hypochlorite to germinal chloroazo compounds 4, generation of the 1-aza-2-azoniaallene cations 5 by action with equimolar antimony pentachloride and interception with nitrile and alkyne molecules by cycloaddition to the triple bond followed by ring enlargement. The structure of the compounds was principally established on the basis of the analytical and spectral data along with the previously published X-ray diffraction analysis on 8a.

This study aimed at the investigation of the reactivity of azocarbenium salts derived from the easily accessible 5α-cholestan-3-one. Novel triazolo-annulated steroidal heterocycles have been successfully constructed.Figure optionsDownload as PowerPoint slideHighlights
► Efficient syntheses of novel steroidal triazoles.
► The [1,2,4]-triazolo-annulated 3-aza-A-homocholestane products represent unprecedented steroidal heterocycles.
► The structures of all novel compounds were confirmed by NMR measurements.
► The involved ring expansion occurs with complete regioselectivity.