The reaction of azoles with 17-chloro-16-formylandrosta-5,16-dien-3β-yl-acetate: Synthesis and structural elucidation of novel 16-azolylmethylene-17-oxoandrostanes

The synthesis and structural elucidation, by 1D and 2D NMR and X-ray diffraction techniques, of novel E/Z 16-azolylmethylene-17-oxoandrostanes 2–9 prepared from the Vilsmeier–Hack reaction product 17-chloro-16-formylandrosta-5,16-dien-3β-yl acetate 1 is reported. The reaction proceeds with pyrrole and pyrrole-alike nitrogen heterocycles such as 7-azaindole, indole, and 3-methylindole, in DMF, at 80 °C, in the presence of K2CO3, and allowed the attachment of privileged heterocyclic moieties, through the nitrogen atom to the steroid core at C16 via a methine carbon bridge, which is unprecedented in the literature and of potential synthetic and biological interest. Considerations on the possible reaction mechanism are included. All the synthesized compounds are new and are currently being tested for biological activities.

Figure optionsDownload as PowerPoint slideHighlights
► The Vilsmeir-Hack reaction product 17-chloro-16-formylandrosta-5,16-dien-3β-yl acetate reacts with pyrrole and pyrrole-alike heterocycles to afford novel E/Z 16-azolylmethylene-17-oxo androstanes.
► The novel compounds bear privileged heterocyclic moieties attached through the nitrogen atom to the steroid core at C16 via a methine carbon bridge.
► Considerations on the mechanism of the reaction are provided.
► Full structural elucidation of the compounds has been performed by 1D and 2D NMR and X-ray diffraction techniques.