1035-77-4Relevant articles and documents
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.
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.
Total synthesis of optically active steroids, II. Total synthesis of natural estradiol methyl ether
Rufer,Schr?der,Gibian
, p. 206 - 216 (1967)
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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.
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.
Homogeneous and heterogeneous catalytic asymmetric reactions II. Asymmetric hydrogenation of steroid ketones
Goendoes, Gyoergy,Gera, Lajos,Bartok, Mihaly,Orr, James C.
, p. 365 - 376 (1989)
The asymmetric reduction of steroid 17- and 20-ketones with chiral hydrosilanerhodium-(+)-and (-)-diop-complex catalysts allows different stereoselectivities in the formation of 17-alcohols, but not of 20-alcohols.The degree of this stereoselectivity is higher than that attained with other methods.The stereoselectivity can be explained in terms of the most preferred conformation of the α-siloxysteroid-rhodium intermediate complexes.
Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents
Alsayari, Abdulrhman,Kopel, Lucas,Ahmed, Mahmoud Salama,Pay, Adam,Carlson, Taylor,Halaweish, Fathi T.
, p. 32 - 40 (2017)
Series of estrone based analogs were synthetically investigated at positions C-9, C-11, C-16, and C-17 positions, to be biologically evaluated via assessment of cell proliferation, cytotoxicity, and estrogenic/anti-estrogenic activity. LA-7 and LA-10 revealed their potential to exhibit inhibitory estrogenic profile. This was further validated by Estrogen Receptor-α (ER-α) and Estrogen Receptor-β (ER-β) competitive binding assays to reveal the high selective affinity of LA-7 towards ER-α at 5.49 μM, while LA-10 did not show any binding affinity towards neither ER-α nor ER-β; suggesting another mechanism for inhibition. This was validated by in silico molecular docking simulations of LA-7 to reveal the optimum binding affinity of LA-7 towards ER-α.
Proton acid-catalysed transformations of estrogen derivatives: New results and some mechanistic aspects of the Kober colour reaction
Pindur,Schall
, p. 637 - 642 (1994)
The 3-O-methylated estrogen derivatives 1a-d and α-estradiol (1e) underwent sulfuric acid-catalysed transformations to furnish the steroids 2-6. The processes involved in the reaction sequence are regioselective sulfonation and, above all, the Wagner-Meerwein rearrangement of the methyl group at C-13. With the objective of obtaining further information on the course of the Kober colour reaction of estrogens, some UV/VIS and ESR spectroscopic investigations were also carried out.
Hemilabile Benzyl Ether Enables Γ-C(sp3)-H Carbonylation and Olefination of Alcohols
Tanaka, Keita,Ewing, William R.,Yu, Jin-Quan
supporting information, p. 15494 - 15497 (2019/10/16)
Pd-catalyzed C(sp3)-H activation of alcohol typically shows β-selectivity due to the required distance between the chelating atom in the attached directing group and the targeted C-H bonds. Herein we report the design of a hemilabile directing group which exploits the chelation of a readily removable benzyl ether moiety to direct Γ- or δ-C-H carbonylation and olefination of alcohols. The utility of this approach is also demonstrated in the late-stage C-H functionalization of β-estradiol to rapidly prepare desired analogues that required multi-step syntheses with classical methods.
