10587-75-4Relevant academic research and scientific papers
Production of 16β-(acetoxy)acetoxy derivatives by reaction of 17-keto steroid enol acetates with lead (IV) acetate
Numazawa, Mitsuteru,Shelangouski, Momoko,Nakakoshi, Masamichi
, p. 743 - 748 (2001)
Treatment of enol acetates of 3β-acetoxyandrost-5-en-17-one and its 5α-reduced analog, 5α-androstan-17-one, and estrone acetate, 1-4, with Pb(OCOCH3)4 in acetic acid and acetic anhydride gave the previously unreported products, 16β-(acetoxy)acetoxy-17-ketones 8-10 and 12, in 9-15% yields along with the known major products, 16β-acetoxy-17-ketones 5-7 and 11. Similar treatment of the 16β-acetoxy-17-ketones with the lead reagent did not yield the corresponding (acetoxy)acetates. Reaction of the enol acetate 3 with Pb(OCOCD3)4 in CD3COOD yielded principally the labeled (acetoxy)acetate 10-d3, which had a CD3COOCH2COO moiety at C-16β. In contrast, when the deuterated enol acetate 3-d3, which was obtained by treatment of the 17-ketone 14 with (CD3CO)2O in the presence of LDA and which had a CD3COO moiety at C-17, was reacted with Pb(OCOCH3)4, the resulting product was the labeled compound 10-d2. This product had a CH3COOCD2COO function at C-16β. Based on these results, along with further isotope-labeling experiments, it seems likely that the (acetoxy)acetate is produced through a lead (IV) acetate-catalyzed migration of the 17-acetyl function of the enol acetate to the C-16β-position followed by attack of an acetoxy anion of the lead reagent. Copyright
C19-Steroids as androgen receptor modulators: Design, discovery, and structure-activity relationship of new steroidal androgen receptor antagonists
Marwah, Padma,Marwah, Ashok,Lardy, Henry A.,Miyamoto, Hiroshi,Chang, Chawnshang
, p. 5933 - 5947 (2007/10/03)
Dehydroepiandrosterone (DHEA), the most abundant steroid in human circulating blood, is metabolized to sex hormones and other C19-steroids. Our previous collaborative study demonstrated that androst-5-ene-3β,17β-diol (Adiol) and androst-4-ene-3,17-dione (Adione), metabolites of DHEA, can activate androgen receptor (AR) target genes. Adiol is maintained at a high concentration in prostate cancer tissue; even after androgen deprivation therapy and its androgen activity is not inhibited by the antiandrogens currently used to treat prostate cancer patients. We have synthesized possible metabolites of DHEA and several synthetic analogues and evaluated their role in androgen receptor transactivation to identify AR modulators. Steroids with low androgenic potential in PC-3 cell lines were evaluated for anti-dihydrotestosterone (DHT) and anti-Adiol activity. We discovered three potent antiandrogens: 3β-acetoxyandrosta-1,5-diene-17-one 17-ethylene ketal (ADEK), androsta-1,4-diene-3,17-dione 17-ethylene ketal (OAK), and 3β-hydroxyandrosta-5,16-diene (HAD) that antagonized the effects of DHT as well as of Adiol on the growth of LNCaP cells and on the expression of prostate-specific antigen (PSA). In vivo tests of these compounds will reveal their potential as potent antiandrogens for the treatment of prostate cancer.
