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 1H and 13C spectra are reported herein. Finally, the effects of the synthesized amphiphilic steroid derivatives on the proliferation of cancer cells are reported and discussed.

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► Novel amphiphilic enantiopure steroid derivatives.
► Barbier-allylation – ring-closing metathesis – dihydroxylation sequence.
► Completely characterized 1H and 13C NMR spectra.
► Notable differences in growth inhibition of cancer cell lines.
► Outstanding starting points for further structural design.