Microwave assisted preparation of C(1)-C(11) oxygen-bridged pregnanes

SONEGO, JUAN M.; ALVAREZ, LAUTARO D.; VELEIRO, ADRIANA S.; BURTON, GERARDO

Beijing

Simposio; Tetrahedron Symposium 2010; 2010

The introduction of oxygen bridges involving selected carbons of the steroid nucleus produces major changes in the overall shape of steroid molecules, resulting in rigid structures. These structures allow us to evaluate with minimal functional change, the influence of conformation in the biological activity. Previously we have synthesized a series of 1,11-epoxysteroids using an intramolecular remote functionalization reaction with Suarez reagent (diacetoxyiodobenzene/I2, irradiation with visible light).[1,2] We report here that photolysis with visible light can be replaced by microwave  irradiation to prepare 1,11-oxygen bridges.Both methodologies were compared when the reaction was tried on the readily available 11-alpha-hydroxypregnanes (1-3). The results obtained were similar for compounds 1 and 2. However, when we tried the reaction on compound 3, reaction time, reproducibility and yield were significantly improved when using microwave irradiation. We also explored the possibility of using the 1,11-epoxypregnanes as intermediates to introduce a substituent at a non-functionalized C-1 of the steroid nucleus. For example, we prepared compounds 5 and 6 from 1, by cleavage of the 1,11-oxygen bridge of 4 with zinc iodide. The outcome of the reaction under different conditions may be explained using molecular modelling methods, in terms of the relative energies of the 1-iodo intermediates.