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 K(2)CO(3), 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.