4229-69-0

Herein, we report an efficient construction of the lactone bridge of strongylophorine-2, which is a meroditerpenoid isolated from Strongylophora durissima and an inhibitor for HIF-1 transcriptional pathway. Starting from dehydroepiandrosterone acetate, the characteristic lactone has been constructed in 5.4% over 18 steps by employing, (1) modified oxy radical-mediated C–H functionalization at the C24 methyl group, and (2) four-step manipulation of C4 quaternary carbon stereogenic center. The lactone synthesized here is expected as a precursor for (8-desmethyl)strongylophorine-2 which is of particular interest in terms of structure–activity relationships in the inhibition of HIF-1 transcriptional pathway.

The invention features compounds, pharmaceutical compositions and methods useful for the treatment of neoplasia. In particular embodiments, the compounds of the invention are useful for the treatment of multidrug resistant neoplasia.

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Derivatives of 19-oxygenated-5α-androstanes are described which are useful in enhancing the libido and related psychic attitudes in mammals.

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