Steroid-based head-to-tail amphiphiles as effective iono- and protonophores

The synthesis of five steroid-oligo(ethyleneglycol) conjugates (1-5) has been accomplished starting from commercially available epi-androsterone (8) and known 3 beta-[(tert-butyidiphenylsilyl)oxy]-5 alpha-23,24-bisnorchol-16-en-6 alpha,7 beta,22-triol (27). The synthetic strategy was based on a convergent approach including stereoselective C- 17 side chains construction and standard coupling reactions. The activities of the head-to-tail amphiphiles, once incorporated in 95:5 egg PC/PG vesicular membranes, have been assessed by direct determination of transported species by NMR techniques (Na-23(+)) and fluorescence spectroscopy (H+). The sodium and proton transmembrane transport was compared to those evaluated for the polyene macrolide antibiotic amphotericin B and those shown by the known related C-2-symmetric sterolpolyether conjugates 6 and 7. (c) 2005 Elsevier Ltd. All rights reserved.