Increasing the amphiphilicity of an estradiol based steroid structure by Barbier-allylation - ring-closing metathesis - dihydroxylation sequence

Polyhydroxylated steroids, such as brassinosteroids, phytoecdysteroids and steroid saponins, are structurally attractive compounds possessing a number of interesting biological properties. Accordingly, development of synthetic procedures to build steroid based structures mimicking the naturally occurring hydrophilic steroids is of topical interest. In the present work, a D-secoestrone derivative was modified further by Barbier-allylation - ring-closing metathesis - dihydroxylation sequence with the aim to prepare steroid based structures with limited hydrophilicity. A straightforward synthesis route was developed with the isolated yield for each step ranging from good to excellent. All compounds prepared were fully characterized by NMR spectroscopic techniques and completely assigned H-1 and C-13 spectra are reported herein. Finally, the effects of the synthesized amphiphilic steroid derivatives on the proliferation of cancer cells are reported and discussed. (C) 2011 Elsevier Inc. All rights reserved.