Synthesis of 19-hydroxy-1β,19-cyclosteroids

Model Studies Towards Azadirachtin: Part 2. Construction of the Crowded C8bC14 Bond by Transition Metal Chemistry We thank Drs. D. H. Huang and G. Siuzdak for NMR spectroscopic and mass spectrometric assistance, respectively. This work was financially supported by the National Institutes of Health (USA), the Skaggs Institute for Chemical Biology, a predoctoral fellowship from the Division of Organic Chemistry of the American Chemical Society sponsored by Novartis (to A.J.R.), postdoctoral fellowships from

“…Synthesis of the required decalin fragment 17 commenced with benzylation of the known alcohol 5 3 under acidic conditions to afford 6 in 73 % yield. The resulting ketone 6 was then regioselectively brominated with benzyltrimethylammonium tribromide, and the intermediate α ‐bromoketone was heated in DMF in the presence of LiBr and Li 2 CO 3 at 110 °C to furnish enone 7 in 95 % overall yield through elimination of HBr 4. Hydroxylation of 7 was accomplished upon treatment with KHMDS followed by the addition of Davis oxaziridine5 8 to exclusively afford equatorial alcohol 9 in 60 % yield.…”

Steroids: reactions and partial synthesis

“…96 Derivatives of androst-5-ene-7,17-dione 43 have also been studied as inhibitors of aromatase. 97 Various 19-hydroxy-5b,19-cyclosteroids 98 and 19-hydroxy-1b,19-cyclosteroids 99 have been synthesized by reductive cyclization of 19-formyl-4-en-3-ones (44?45) and 19-formyl-1-en-3-ones (46?47) and their biological activity has been examined in this context. The ring opening reactions of these 5b,19-cyclosteroids have been studied.…”

Developing steroidal aromatase inhibitors-an effective armament to win the battle against breast cancer

“…The 6,7-aziridines and their N-substituted derivatives were found to have poor to moderate aromatase inhibition, while 7α-acetoxy-6β-azidoandrost-4-ene-3,17-dione 215 was found to be a potent aromatase inhibitor with an IC 50 value of 0.4 µM [161]. A series of various (19R/S)-hydroxy-1β,19-cycloandrostane-3,17-diones have been reported by Templeton et al(Figure 62) The 19R-ketone/hemiketal 216a/217 and the 19R-acetate 216b showed 40 -50 % inhibition of aromatase [162]. Keeping in mind the importance of the planarity of steroidal A-ring for potent aromatase inhibitory activity, a series of 4-hydroxyandrostenedione (formestane, 4) and testolactone (3) derivatives have been reported by Cepa et al(Figure 63).…”