1839-54-9Relevant articles and documents
Reaction of trimethylsilylimidazole with 5,10β-epoxy-3-ketosteroids: Enolization and aromatization of the A-ring
Kulkarni, S.,Abdel-Baky, S.,Quesne, P. W. Le,Vouros, Paul
, p. 131 - 148 (1989)
The reaction of trimethylsilylimidazole (TSIM) and 3-keto-5,10-epoxy-nor-19-methylandrostanone 3 and its 17-acetate analog 4 was examined at two different temperatures.In both compounds, reaction at 90 deg C gave predominantly a Δ3-silyl-enol ether plus a minor product as a result of the epoxide ring opening.Under reflux conditions, besides the aforementioned products, aromatization of the A-ring was observed as a major process.The results suggest the potential use of silylation reactions with epoxyketones towards the synthesis of aromatic compounds.
The metabolism of 16-fluoroestradiols in vivo: Chemical strategies for restricting the oxidative biotransformations of an estrogen-receptor imaging agent
Stalford, Anne C.,Maggs, James L.,Gilchrist, Thomas L.,Park, B. Kevin
, p. 750 - 761 (2007/10/03)
16α-Fluoro-17β-, 16α-fluoro-17α-, and 16β-fluoro-17β-[6,7- 3H]estradiol were prepared from [6,7-3H]estrone via fluorination of 3,17- bis(tert-butyldimethylsilyloxy)-[6,7-3H]estratetraene with N- fluoropyridinium triflate and reduction of 16α/β-fluoro[6,7-3H]estrone with NaBH4. The three isomers were separated by silica-phase high- performance liquid chromatography. They were administered intravenously (4 μmol/kg) to anaesthetized male rats. Their biliary metabolites (90-97% of dose over 6 h) were characterized by high performance liquid chromatography- mass spectrometry and compared with those of [6,7-3H]17β-estradiol. The four estrogens and their hydroxylated and methoxylated metabolites were excreted as glucuronides. C-16 fluorination blocked C-16 hydroxylation and also the dehydrogenation of the C-17 hydroxyl group. The 16α-17β isomer was extensively glucuronylated at C(O)3 but also underwent aromatic hydroxylation and methoxylation before conjugation. Its C-17 epimer was subject to much greater aromatic hydroxylation but the catecholestrogen was O-methylated to a greater relative extent. The 16β-17β derivative underwent alicyclic as well as substantial aromatic hydroxylation and yielded numerous isomeric glucuronides of O-methylated catechols. Thus, the fluorine exerted complex effects (inhibitory and enhancing) on both localized (D-ring) and distal (A- ring) biotransformations of the estradiol molecule; the direction and magnitude of the effects being dependent upon the stereochemistry at C-16 and C-17. These findings provide structural guidelines for restricting the metabolism of tumor-imaging fluoroestrogens and thereby enhancing their deliver), to the target tissue.
