6193-99-3Relevant academic research and scientific papers
Novel Insertion, Rearrangement and Addition Products from Dihalogenocarbene Reactions with 5(10)-Unsaturated Steroids
Templeton, John F.,Ling, Yangzhi,Lin, Weiyang,Pitura, Randy J.,Marat, Kirk,Bridson, John N.
, p. 1149 - 1158 (2007/10/02)
Novel insertion, rearrangement and addition products from dibromocarbene and dichlorocarbene reactions with 5(10)-unsaturated steroids have been identified.The dihalogenocarbenes were prepared under phase-transfer conditions (CHBr3- or CHCl3-NaOH), and from CHBr3-KOBut-Et2O, phenyl(trichloromethyl)mercury and sodium trichloroacetate.Evidence that the major products arise from an initial dihalogenocarbene reaction on the α face of the molecule is reported.The major products obtained from addition of CBr2 to 3,17-disubstituted estr-5(10)-enes, after ketal hydrolysis, were 19(S)-bromo-9α,19-cyclo-10α-androst-4-en-3-one and 3',3',19(S)-tribromo-3'H-9α,19-cyclopropa-5β,10α-androstan-3-one derivatives together with the 19,19-dibromo-5α,19-cyclo-10α-steroid adduct.No products from addition of CBr2 to the β-face of the double bond, as previously reported, were identified.Reactions of CCl2 gave, besides rearrangement products analogous to those obtained from CBr2, a 5α-hydroxy-9α,19α-cycloandrostane derivative, the 9α-CHCl2 insertion derivative and both α- and β-face addition products to the double bond.Structures were established by homonuclear and heteronuclear correlation and nuclear Overhauser effect NMR measurements and X-ray crystallography.
Fluorine-18-Labeled Progestin Ketals: Synthesis and Target Tissue Uptake Selectivity of Potential Imaging Agents for Receptor-Positive Breast Tumors
Kochanny, Monica J.,VanBrocklin, Henry F.,Kym, Philip R.,Carlson, Kathryn E.,O'Neil, James P.,et al.
, p. 1120 - 1127 (2007/10/02)
We have studied two new fluorine-substituted progestins as potential imaging agents for progesterone-receptor-positive human breast tumors. The steroids are 16α,17α-fluoroacetophenone ketals of 16α,17α-dihydroxyprogesterone and 16α,17α,21-trihydroxy-19-norprogesterone. Synthesis of the latter compound in seven steps from 19-norandrost-4-ene-3,17-dione is reported. Both compounds demonstrate high affinity for the progesterone receptor (PgR) (52.5 and 240percent, respectively, relative to R5020 = 100). The syntheses were adapted to 18F-labeling with 4'--fluoroacetophenone, prepared from 4'-nitroacetophenone by nucleophilic substitution with K18F/Kryptofix. Considerable adjustment of reaction conditions was required to effect ketalization using tracer quantities of the ketone. In tissue distribution studies in estrogen-primed immature female rats, both ketals showed selective uterine uptake, which was blocked by coinjection of a saturating dose of the unlabeled progestin ORG 2058. Additionally, metabolic stability of the radiolabel was indicated by the low radioactivity levels seen in bone. Both compounds showed relatively high uptake in fat, in accord with their relative lipophilicities demonstrated by HPLC-derived octanol-water partition coefficients. The selective uterine uptake and metabolic stability of these compounds suggests that this class of PgR ligands might be promising for the selective imaging of receptor-positive tumors if derivatives of reduced lipophilicity can be prepared.
