1639-43-6Relevant articles and documents
Synthesis of novel C17 steroidal carbamates. Studies on CYP17 action, androgen receptor binding and function, and prostate cancer cell growth
Moreira, Vania M.A.,Vasaitis, Tadas S.,Guo, Zhiyong,Njar, Vincent C.O.,Salvador, Jorge A.R.
, p. 1217 - 1227 (2008)
We have exploited the reaction of 1,1′-carbonylbis(2-methylimidazole) (CBMI) with several 17β-hydroxy androstanes to synthesize a series of novel C17 steroidal carbamates. Structural elucidation features have been provided for the final compounds based on 1D and 2D NMR techniques, IR spectroscopy, and related literature. The new compounds were tested for inhibition of human cytochrome 17α-hydroxylase-C17,20-lyase (CYP17) and androgen receptor (AR) binding and function effects. Their inhibitory potential against PC-3 cell proliferation was also evaluated. Compounds 11 and 23 were found to inhibit CYP17 with IC50 values of 17.1 and 11.5 μM, respectively. The carbamate moiety at C17 allowed tight binding of the synthesized compounds to both wild-type (wt-) and mutated AR. When bound to the mutated AR, the compounds were found to have a dual effect, stimulating transcription at low concentrations while almost fully blocking it at the higher concentrations tested, in the presence of the natural androgen dihydrotestosterone (DHT). Compounds 8 and 12 were the most active against PC-3 cell proliferation with EC50 values of 2.2 and 0.2 μM, respectively.
Reduction of steroidal ketones and enones by sodium dithionite in presence of phase transfer catalyst
Akamanchi,Patel,Meenakshi
, p. 1655 - 1660 (1992)
Sodium dithionite has been effectively used in the reduction of steroidal ketones and enones with remarkable selectivity and high yields under phase transfer catalysis (PTC) conditions to give alcohols and ketones respectively. An application of these selectivities is demonstrated by reducing an important steroid intermediate 16-dehydropregnenolone acetate to pregnenolone acetate in very high yields.
Epimerization of Tertiary Carbon Centers via Reversible Radical Cleavage of Unactivated C(sp3)-H Bonds
Wang, Yaxin,Hu, Xiafei,Morales-Rivera, Cristian A.,Li, Guo-Xing,Huang, Xin,He, Gang,Liu, Peng,Chen, Gong
supporting information, p. 9678 - 9684 (2018/07/21)
Reversible cleavage of C(sp3)-H bonds can enable racemization or epimerization, offering a valuable tool to edit the stereochemistry of organic compounds. While epimerization reactions operating via cleavage of acidic C(sp3)-H bonds, such as the Cα-H of carbonyl compounds, have been widely used in organic synthesis and enzyme-catalyzed biosynthesis, epimerization of tertiary carbons bearing a nonacidic C(sp3)-H bond is much more challenging with few practical methods available. Herein, we report the first synthetically useful protocol for the epimerization of tertiary carbons via reversible radical cleavage of unactivated C(sp3)-H bonds with hypervalent iodine reagent benziodoxole azide and H2O under mild conditions. These reactions exhibit excellent reactivity and selectivity for unactivated 3° C-H bonds of various cycloalkanes and offer a powerful strategy for editing the stereochemical configurations of carbon scaffolds intractable to conventional methods. Mechanistic study suggests that the unique ability of N3? to serve as a catalytic H atom shuttle is critical to reversibly break and reform 3° C-H bonds with high efficiency and selectivity.
Synthesis and antiproliferative activity of some androstene oximes and their O-Alkylated derivatives
Acharya, Pratap Chandra,Bansal, Ranju
, p. 193 - 199 (2014/03/21)
In order to study the structure-activity relationship with respect to the cytotoxicity of steroidal oximes, several 6E-hydroximino-4-ene steroids and their O-alkylated derivatives were synthesized. The oxime ethers were solidified and purified by preparing their corresponding oxalate salts. The new derivatives as well as some previously synthesized ones were evaluated for in vitro antineoplastic activity against a panel of 60 cancer cell lines at 10 μM. The oximes and oxime ethers were found to have moderate to good antiproliferative activity against various leukemia, colon, melanoma, and renal cancer cell lines. Several 6E-hydroximino-4-ene steroids and their O-alkylated derivatives were synthesized. Their structure-activity relationship with respect to the cytotoxicity of steroidal oximes was studied. The oximes and oxime ethers were found to have moderate-to-good antiproliferative activity against various leukemia, colon, melanoma, and renal cancer cell lines.
