1035-77-4Relevant academic research and scientific papers
Synthesis and structure-activity profiles of A-homoestranes, the estratropones
Miller, Thomas A.,Bulman, Amanda L.,Thompson, Charles D.,Garst, Michael E.,Macdonald, Timothy L.
, p. 3836 - 3841 (1997)
2-Methoxyestradiol, a mammalian metabolite of estradiol, has reported antiangiogenic activity which has been proposed to be mediated through interaction at the colchicine binding site on the tubulin monomer. Subsequent structure-activity studies of 2-methoxyestradiol have yielded highly potent steroidal inhibitors of tubulin polymerization. In an effort to probe the scope of binding at the colchicine binding site and the nature of the relationship between 2-methoxyestradiol and colchicine, a series of colchicine/2-methoxyestradiol hybrids was synthesized. These A-homoestrane hybrid systems, collectively termed estratropones, possessed an A-ring tropone system with the keto functionality at either the C-2, C-3, or C-4 position of the steroid nucleus. The estratropones were evaluated for their ability to inhibit the polymerization of tubulin using an in vitro purified bovine brain assay. Most of these hybrids inhibit polymerization with greater potency than either of the natural products. The most potent of these congeners possessed an approximate 5-fold enhancement of the activity of colchicine for the inhibition of tubulin polymerization. α-Substituents on the tropone ring showed varied effects on the activities for the two classes of estratropones studied in this regard, the C-3 oxo and the C-4 oxo species. The 3-substituted 4-oxoestratropones exhibited antitubulin activity according to Cl ? Br > OCH3, whereas the 4-substituted 3-oxoestratropones exhibited activity according to OCH3 > Br ? Cl. It is unclear if these substituent factors are purely electronic or steric effects or if the substituent operates indirectly by altering the conformation of the nonplanar troponoid ring. The estratropones represent a new class of tubulin binding agents with potential antiangiogenic utility.
Pot Economy in the Total Synthesis of Estradiol Methyl Ether by Using an Organocatalyst
Hayashi, Yujiro,Koshino, Seitaro,Ojima, Kanna,Kwon, Eunsang
, p. 11812 - 11815 (2017)
Enantioselective total synthesis of estradiol methyl ether has been accomplished in a pot-economical manner using five reaction vessels and four purifications. The key reaction is a diphenylprolinol silyl ether mediated domino Michael/aldol reaction to afford bicyclo[4.3.0]nonane derivatives, containing the A, C, and D rings of steroids, as a single isomer with excellent enantioselectivity. Six reactions such as oxidation, hydrogenation, formation of acid chloride, Friedel–Crafts reaction, deprotection, and reduction can be carried out in the last one-pot sequence.
Facile cleavage of ethers in ionic liquid
Cheng, Lili,Aw, Carlin,Ong, Siew Siang,Lu, Yixin
, p. 2008 - 2010 (2007)
Various alkyl ethers were efficiently cleaved by treating them with pyridinium halides in ionic liquid, and the desired products were obtained in excellent yields.
The synthesis and evaluation of functionalized estratropones: Potent inhibitors of tubulin polymerization
Miller, Thomas A.,Bulman, Amanda L.,Thompson, Charles D.,Garst, Michael E.,Macdonald, Timothy L.
, p. 1851 - 1856 (1997)
The synthesis of several ex-substituted estratropones is described. The compounds were evaluated for the inhibition of tubulin polymerization using purified bovine brain tubulin. Several of the compounds are equipotent to colchicine for their ability to inhibit the polymerization of tubulin.
Ir(III)-Catalyzed Carbocarbation of Alkynes through Undirected Double C-H Bond Activation of Anisoles
Romanov-Michailidis, Fedor,Ravetz, Benjamin D.,Paley, Daniel W.,Rovis, Tomislav
, p. 5370 - 5374 (2018)
A novel, electron-deficient cyclopentadienyl iridium(III) catalyst enables sequential cleavage of arene C(sp2)-H and methoxy C(sp3)-H bonds of anisoles, generating reactive metalacycles that insert difluoroalkynes to afford chromenes under mild reaction conditions. This transformation is an arylalkylation of an alkyne-a carbocarbation-via a nonchelate-assisted cleavage of two C-H bonds.
Convenient O-methylation of phenols with dimethyl carbonate
Lee, Youngmin,Shimizu, Isao
, p. 1063 - 1064 (1998)
Reaction of phenols in dimethyl carbonate in the presence of cesium carbonate at 120-160° C gave aryl methyl ethers in good yields, whereas the reaction of aliphatic alcohols gave the corresponding alkyl carbonates. This method provides a useful synthetic method for preparation of various aryl methyl ethers without using toxic methyl iodide or dimethyl sulfate. O-Methylation of the aromatic hydroxy group of estradiol was carried out in 2 steps without protection of the alcoholic hydroxy group in the same molecule.
Multistep Synthesis and in Vitro Anticancer Evaluation of 2-Pyrazolyl-Estradiol Derivatives, Pyrazolocoumarin-Estradiol Hybrids and Analogous Compounds
Adamecz, Dóra Izabella,Frank, éva,Kiricsi, Mónika,Krishna Gopisetty, Mohana,Molnár, Barnabás
, (2020)
Although the hormone independent cytotoxic activity of several estradiol derivatives endowed with a simple substituent at C-2 has been reported so far, 2-heterocyclic and 2,3-condensed analogs are less investigated from both synthetic and pharmacological points of view. Therefore, novel A-ring-connected 2-pyrazoles of estradiol and, for comparison, their structurally simplified non-steroidal pairs were synthesized from estradiol 3-methyl ether and 6-methoxy-1,2,3,4-tetrahydronaphthalene. Friedel-Crafts acetylation of the protected phenolic compounds and subsequent O-demethylation led to ortho-substituted derivatives regioselectively, which were converted to arylhydrazones with phenylhydrazine, 4-tolylhydrazine and 4-chloro-phenylhydrazine, respectively, under microwave conditions. The hydrazones were subjected to cyclization with the Vilsmeier-Haack reagent immediately after preparation and the ring closure/formylation sequence resulted in steroidal and non-steroidal 40-formylpyrazoles in moderate to good yields. During reductive transformations, 4-hydroxymethyl-pyrazoles were obtained, while oxidative lactonization of the 4-formylpyrazole moiety with the phenolic OH in the presence of the Jones reagent afforded A-ring-integrated pyrazolocoumarin hybrids and related analogs. Steroidal pyrazoles, which were produced as C-17 acetates due to acetylation of C-17 OH during the primary Friedel-Crafts reaction, underwent deacetylation in alkaline methanol to furnish 2-heterocyclic estradiol derivatives. Pharmacological studies revealed the overall and cancer cell-specific cytotoxicity of the derivatives and the half maximal inhibitory concentrations were obtained for the most promising compounds.
11β-alkyl-Δ9-19-nortestosterone derivatives: High-affinity ligands and potent partial agonists of the androgen receptor
Muddana, Smita S.,Price, Aimee M.,MacBride, Megan M.,Peterson, Blake R.
, p. 4985 - 4988 (2004)
We report the synthesis of novel steroidal androgen receptor ligands comprising 11β-alkyl-Δ9-derivatives of 19-nortestosterone. These compounds are structurally related to the antiprogestin, antiglucocorticoid, and antiandrogen drug mifepristone (RU486). Nortestosterone analogues bearing 11β-octyl and 11β-decyl side-chains bind tightly to recombinant AR protein (IC50 = 6.6 nM and IC50 = 0.8 nM), block AR dimerization, exhibit activity against LNCaP prostate cancer cells, and comprise partial AR agonists with low antiglucocorticoid activity.
Total Synthesis of Estradiol Methyl Ether and Its Five-Pot Synthesis with an Organocatalyst
Koshino, Seitaro,Kwon, Eunsang,Hayashi, Yujiro
, p. 5629 - 5638 (2018)
Enantioselective total synthesis of estradiol methyl ether has been accomplished in a highly diastereo- and enantioselective manner. The key reaction is diphenylprolinol silyl ether mediated domino Michael/aldol reaction to afford bicyclo[4.3.0]nonane derivatives with A, C, and D rings of the steroids as a single isomer with excellent enantioselectivity. Each reaction was optimized, and the total synthesis could be accomplished in 12 pots with 10 purifications using silica gel, resulting in an overall yield of 6.8 %. The reaction sequence and reaction conditions were then optimized in terms of pot economy, whereupon estradiol methyl ether could be synthesized using five reaction vessels with four purifications in an overall yield of 15 %. Notably, six reactions, namely, oxidation, hydrogenation, formation of acid chloride, Friedel–Crafts reaction, deprotection, and reduction could be carried out in the last one-pot sequence.
A simple, convenient and chemoselective formylation of sterols by Vilsmeier reagent
Srivastava, Vandana,Negi, Arvind Singh,Kumar,Gupta
, p. 632 - 638 (2006)
Vilsmeier reagent (DMF-POCl3) was used as an efficient formylating agent. Several sterols having sec-hydroxyl group at 3/17-position have been modified into respective formate esters. The method is simple, mild, chemoselective and provides sec-alcoholic protection in good yields.
