- Synthesis and structure-activity profiles of A-homoestranes, the estratropones
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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.
- Miller, Thomas A.,Bulman, Amanda L.,Thompson, Charles D.,Garst, Michael E.,Macdonald, Timothy L.
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- Pot Economy in the Total Synthesis of Estradiol Methyl Ether by Using an Organocatalyst
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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.
- Hayashi, Yujiro,Koshino, Seitaro,Ojima, Kanna,Kwon, Eunsang
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- Facile cleavage of ethers in ionic liquid
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Various alkyl ethers were efficiently cleaved by treating them with pyridinium halides in ionic liquid, and the desired products were obtained in excellent yields.
- Cheng, Lili,Aw, Carlin,Ong, Siew Siang,Lu, Yixin
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- The synthesis and evaluation of functionalized estratropones: Potent inhibitors of tubulin polymerization
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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.
- Miller, Thomas A.,Bulman, Amanda L.,Thompson, Charles D.,Garst, Michael E.,Macdonald, Timothy L.
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- Ir(III)-Catalyzed Carbocarbation of Alkynes through Undirected Double C-H Bond Activation of Anisoles
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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.
- Romanov-Michailidis, Fedor,Ravetz, Benjamin D.,Paley, Daniel W.,Rovis, Tomislav
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- Convenient O-methylation of phenols with dimethyl carbonate
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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.
- Lee, Youngmin,Shimizu, Isao
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- Multistep Synthesis and in Vitro Anticancer Evaluation of 2-Pyrazolyl-Estradiol Derivatives, Pyrazolocoumarin-Estradiol Hybrids and Analogous Compounds
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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.
- Adamecz, Dóra Izabella,Frank, éva,Kiricsi, Mónika,Krishna Gopisetty, Mohana,Molnár, Barnabás
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- 11β-alkyl-Δ9-19-nortestosterone derivatives: High-affinity ligands and potent partial agonists of the androgen receptor
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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.
- Muddana, Smita S.,Price, Aimee M.,MacBride, Megan M.,Peterson, Blake R.
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- Total Synthesis of Estradiol Methyl Ether and Its Five-Pot Synthesis with an Organocatalyst
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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.
- Koshino, Seitaro,Kwon, Eunsang,Hayashi, Yujiro
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- A simple, convenient and chemoselective formylation of sterols by Vilsmeier reagent
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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.
- Srivastava, Vandana,Negi, Arvind Singh,Kumar,Gupta
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- Chiral hydrogenation of estrone-3-methyl ether on modified Raney nickel catalysts
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The stereochemistry of reduction of the steroid 17-ketone group by Raney nickel catalyst modified by tartaric acid depends on the chirality of the tartaric acid, the pH, and the pressure of hydrogenation. Keywords: chiral reduction; modified Raney nickel catalyst
- Goendoes, Gyoergy,Wittman, Gyula,Bartok, Mihaly,Orr, James C.
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- Homogeneous and heterogeneous catalytic asymmetric reactions II. Asymmetric hydrogenation of steroid ketones
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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.
- Goendoes, Gyoergy,Gera, Lajos,Bartok, Mihaly,Orr, James C.
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- Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents
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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.
- Alsayari, Abdulrhman,Kopel, Lucas,Ahmed, Mahmoud Salama,Pay, Adam,Carlson, Taylor,Halaweish, Fathi T.
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- Complete 1H and 13C NMR spectral assignment of 17-hydroxy epimeric sterols with planar A or A and B rings.
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Complete 1H and 13C spectral assignments of 17beta- and 17alpha-hydroxy epimers of three biologically active sterols (boldenone, 3-methoxyestradiol and 3-methoxydihydroequilenin) were achieved making use of one- and two-dimensional NMR techniques (1D-HOHAHA, DEPT, COSY, NOESY, TOCSY, HSQC and COLOC). Copyright 2004 John Wiley & Sons, Ltd.
- Ciuffreda,Casati,Manzocchi
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- Proton acid-catalysed transformations of estrogen derivatives: New results and some mechanistic aspects of the Kober colour reaction
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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.
- Pindur,Schall
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Read Online
- Direct Synthesis of α-Amino Nitriles from Sulfonamides via Base-Mediated C-H Cyanation
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Herein, we disclose a transition-metal-free reaction system that enables α-cyanation of sulfonamides through C-H bond cleavage for the preparation of α-amino nitriles, including difficult-to-access all-alkyl α-tertiary scaffolds. More than 50 substrate examples prove a wide functional group tolerance. Additionally, its synthetic practicality is highlighted by gram-scalability and the late-stage modification of natural compounds. Mechanistic experiments suggest that this process involves in situ formation of an imine intermediate via base-promoted elimination of HF.
- Shi, Shasha,Yang, Xianyu,Tang, Man,Hu, Jiefeng,Loh, Teck-Peng
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supporting information
p. 4018 - 4022
(2021/05/26)
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- Hemilabile Benzyl Ether Enables Γ-C(sp3)-H Carbonylation and Olefination of Alcohols
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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.
- Tanaka, Keita,Ewing, William R.,Yu, Jin-Quan
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supporting information
p. 15494 - 15497
(2019/10/16)
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- Hemilabile Benzyl Ether Enables γ-C(sp3)-H Carbonylation and Olefination of Alcohols
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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.
- Tanaka, Keita,Ewing, William R.,Yu, Jin-Quan
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supporting information
(2019/10/22)
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- Total Synthesis of (-)-C/D-cis-Dehydro-3-O-methyl-estradiols
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A convergent synthesis of (-)-dehydro-3-O-methyl-C/D-cis-estradiol started from stereochemically defined substituted optically active 3-(2-arylethyl)-γ-butyrolactones. Regioselective bromination of the anisyl moiety, reductive ring opening of the iodolactone, and protecting-group changes led to a Weinreb amide. This then underwent an intramolecular Grignard reaction closing the B-ring to give a tetralone with defined configuration. Introduction of C-11 through an allyl Grignard addition and subsequent ring-closing metathesis gave a tetrahydro phenanthrene derivative. Oxidation of the side-chain alcohol resulted in the key aldehyde group, and a final samarium-diiodide-mediated reductive D-ring annulation resulted in the generation of the target dehydro-C/D-cis-estradiol derivatives with high stereoselectivity. Structure elucidation was carried out using NOEDS (nuclear Overhauser enhanced differential spectroscopy) analysis on the one hand, and conversion into known 3-O-methyl-13β-estradiols by double-bond hydrogenation on the other. Further efforts to use this estradiol synthetic strategy to generate more complex steroidal natural products and pharmaceutically interesting compounds are in progress.
- Kaluza, Nora M.,Schollmeyer, Dieter,Nubbemeyer, Udo
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supporting information
p. 357 - 366
(2016/02/12)
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- Nickel-catalyzed alkylative cross-coupling of anisoles with grignard reagents via C-O bond activation
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We report nickel-catalyzed cross-coupling of methoxyarenes with alkylmagnesium halides, in which a methoxy group is eliminated. A wide range of alkyl groups, including those bearing β-hydrogens, can be introduced directly at the ipso position of anisole derivatives. We demonstrate that the robustness of a methoxy group allows this alkylation protocol to be used to synthesize elaborate molecules by combining it with traditional cross-coupling reactions or oxidative transformation. The success of this method is dependent on the use of alkylmagnesium iodides, but not chlorides or bromides, which highlights the importance of the halide used in developing catalytic reactions using Grignard reagents.
- Tobisu, Mamoru,Takahira, Tsuyoshi,Morioka, Toshifumi,Chatani, Naoto
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supporting information
p. 6711 - 6714
(2016/06/14)
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- Nickel-Catalyzed Cross-Coupling of Anisoles with Alkyl Grignard Reagents via C-O Bond Cleavage
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Nickel-catalyzed cross-coupling of methoxyarenes with alkyl Grignard reagents, which involves the cleavage of the C(aryl)-OMe bond, has been developed. The use of 1,3-dicyclohexylimidazol-2-ylidene as a ligand allows the introduction of a variety of alkyl groups, including Me, Me3SiCH2, ArCH2, adamantyl, and cyclopropyl. The method can also be used for the alkylative elaboration of complex molecules bearing a C(aryl)-OMe bond.
- Tobisu, Mamoru,Takahira, Tsuyoshi,Chatani, Naoto
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supporting information
p. 4352 - 4355
(2015/09/15)
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- Proton-exchanged montmorillonite-mediated reactions of methoxybenzyl esters and ethers
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Proton-exchanged montmorillonite (H-mont) was found to be an eco-friendly and cost-effective catalyst for the generation of O-methylated quinone methides (QM) from the corresponding p or o-methoxybenzyl esters and ethers. Nucleophilic trapping of the O-methylated QM with arenes, alcohols, 1,3-dicarbonyl compounds, silyl enol ethers, and allylsilanes has been carried out, respectively, leading to eco-friendly benzylation reactions. Using this protocol, H-mont-mediated deprotection of PMB-protected esters and ethers have been realized for the first time. This work would pave the way for further exploration in O-alkylated QM that are of chemical and biological significance.
- Chen, Dongyin,Xu, Chang,Deng, Jie,Jiang, Chunhuan,Wen, Xiaoan,Kong, Lingyi,Zhang, Ji,Sun, Hongbin
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p. 1975 - 1983
(2014/03/21)
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- An easy stereoselective synthesis of 5(10)-estrene-3β,17α-diol, a biological marker of pregnancy in the mare
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5(10)-Estrene-3β,17α-diol is an essential reference material for doping analysis in horse-racing laboratories. It is used to detect misuse, for doping purpose, of the pregnancy status in the mare. Its stereoselective synthesis from 17β-estradiol-3-methyl ether (prepared from estrone or 17β-estradiol) was performed in four steps: (1) Mitsunobu inversion of the 17β-alcohol; (2) Birch reduction of the aromatic ring; (3) stereoselective reduction of the 3-ketone via Noyori asymmetric transfer hydrogenation; (4) chemoenzymatic purification.
- Balssa, Frédéric,Fischer, Michael,Bonnaire, Yves
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- A simple and convenient synthesis of 2-methoxyestradiol from estrone
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A simple and straightforward synthesis of 2-methoxyestradiol have been achieved in nine synthetic steps with 21% of overall yield. Being a convenient process, it can be upscaled to industrial process.
- Prakasham,Shanker, Karuna,Negi, Arvind S.
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scheme or table
p. 467 - 470
(2012/05/19)
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- Rearrangement and fragmentation of estrogen ether ions: New aspects found with Fourier transform ion cyclotron resonance mass spectrometry
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Electrospray ionization mass spectra of several di- and tri-hydroxy-estratriene-ethers, as well as estradiol and estriol, have been investigated by high-resolution mass spectrometry. The fragmentation mechanisms leading to the loss of water molecules from the protonated molecular ion have been rationalized by using protecting groups as well as mass spectrometric means such as collision-induced dissociation and infrared multi-photon dissociation. The unexpected observation of a simultaneous loss of two water molecules from the protonated estradiol ethers and of three water molecules from the protonated estriol ethers has been discussed with respect to varying reaction mechanisms and rearrangements. Results and conclusions derived from them were obtained by adequate deuterated ethers.
- Freudenhammer, Christoph,Grotemeyer, Juergen
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experimental part
p. 489 - 501
(2011/10/31)
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- USE OF alpha,beta -UNSATURATED CARBONYL COMPOUNDS AS QUENCH REAGENTS FOR THE BIRCH REDUCTION
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Use of α,β-unsaturated carbonyl compounds as quench reagents for the Birch reduction.
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Page/Page column 2
(2009/01/20)
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- Synthesis of chalcone derivatives on steroidal framework and their anticancer activities
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Chalcone derivatives on estradiol framework have been synthesized. Some of the derivatives showed potent anticancer activity against some human cancer cell lines. Compounds 9 and 19 showed potent activity against MCF-7, a hormone dependent breast cancer cell line. Chalcone 7 was further modified to the corresponding indanone derivative (19) using the Nazarov reaction, which showed better activity than the parent compound against the MCF-7 breast cancer cell line. Active anticancer derivatives were also evaluated for osmotic hemolysis using the erythrocyte as a model system. It was observed that chalcone derivatives showing cytotoxicity against cancer cell lines did not affect the fragility of erythrocytes and hence may be considered as non-toxic to normal cells.
- Saxena, Hari Om,Faridi, Uzma,Kumar,Luqman, Suaib,Darokar,Shanker, Karuna,Chanotiya, Chandan S.,Gupta,Negi, Arvind S.
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p. 892 - 900
(2008/02/13)
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- AMINOSULPHONYL- OR AMINOSULPHONYLAMINO-SUBSTITUTED PHENYL ESTERS AS ESTRADIOL PRODRUGS
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The invention relates to estradiol prodrugs of general formula (I), in which the group Z is bonded to the steroid. The invention further relates to methods for production thereof, pharamceutical compositions comprising said compounds and use thereof for the production of medicaments with an estrogenic effect.
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Page/Page column 22
(2008/06/13)
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- Combined epimerisation and acylation: Meerwein-ponndorf-verley-oppenauer catalysts in action
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A practical racemisation-epimerisation method for chiral secondary alcohols has been developed. Meerwein-Ponndorf-Verley-Oppenauer catalysts such as neodymium(III) isopropoxide are able to racemise these alcohols with retention of other stereocentres in the molecule. This is particularly useful for the recycling of the undesired products of kinetic resolutions of alcohols. By combination of such a racemisation with an acylation using isopropenyl or ethoxyvinyl esters as acyl donors, a fast straightforward recycling of starting materials may be achieved. The combined epimerisation and acylation process is demonstrated for the steroid estradiol methyl ether.
- Klomp, Dirk,Djanashvili, Kristina,Svennum, Nina Cianfanelli,Chantapariyavat, Nuttanun,Wong, Chung-Sing,Vilela, Filipe,Maschmeyer, Thomas,Peters, Joop A.,Hanefeld, Ulf
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p. 483 - 489
(2007/10/03)
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- Synthesis of bone-targeted oestrogenic compounds for the inhibition of bone resorption
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Syntheses have been realised for several members of a new class of potential bone resorption inhibitors consisting of steroidal oestrogenic compounds linked at the 17 position to a geminal bis(phosphonic acid) moiety through an ester linkage. The approach used has the potential to allow other biologically active compounds to be coupled to the geminal bisphosphonate unit.
- Bulman Page, Philip C,Moore, Jonathan P.G,Mansfield, Ian,McKenzie, Michael J,Bowler, Wayne B,Gallagher, James A
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p. 1837 - 1847
(2007/10/03)
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- Acceleration of the reduction of aldehydes and ketones using Mn(dpm)3 catalyst and phenylsilane in the presence of dioxygen
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Saturated ketones and aldehydes are reduced to alcohols by phenylsilane and Mn(dpm)3(cat) in the presence of dioxygen.
- Magnus, Philip,Fielding, Mark R
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p. 6633 - 6636
(2007/10/03)
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- Transition metal-catalyzed intramolecular [4+2] cycloadditions: Mechanistic and synthetic investigations
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The nickel-catalyzed intramolecular cycloaddition of dienes with unactivatable alkynes is found to proceed under mild conditions while the corresponding Diels-Alder cycloaddition of the same substrates either fails of occurs only under forcing conditions. The nickel-catalyzed cycloaddition is also shown to occur with retention of stereochemistry and is not significantly influenced by electronic effects. Finally, the catalyzed process is shown to be applicable to the synthesis of angularly substituted bicycles, including the CD ring systems of steroids and vitamin D.
- Wender, Paul A.,Smith, Thomas E.
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p. 1255 - 1275
(2007/10/03)
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- Steroid-hindered 17β-tertiary alcohol: Characterization of dehydrated compounds
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Five dehydrated compounds obtained from a tert- butyldimethylsilychloride/imidazole or an aqueous hydrochloric acid treatment of 17α-butyl-3-O-methyl estradiol in refluxing solvent were purified and characterized. Three compounds were obtained from a direct vicinal proton elimination, the two others from a vicinal elimination after migration of methyl-18. Depending on the treatment, the proportions of dehydrated compounds are different. In addition, a general profile of experimental conditions providing a similar mixture of dehydrated compounds was also established for this steroid-hindered 17β-tertiary alcohol.
- Bydal, Patrick,Sam, Kay-Mane,Poirier, Donald
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p. 349 - 353
(2007/10/03)
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- Direct Conversion of 13β-Alkylgonatetraenes into 13β-Alkylgon-4-en-3-ones
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Birch reduction of 8,9-didehydroestradiol-17β 3-methyl ether 1 or 9(11)-didehydroestradiol-17β 3 methyl ether 2 followed by acid hydrolysis results in a mixture of 19-nortestosterone 8 and 19-nor-9β,10α-testosterone 9 in varying amounts.However, reduction of their acetates with sodium or lithium, tert-butyl alcohol in liquid ammonia and in the presence of aniline affords exclusively 19-nortestosterone.Similarly, 18α-homo-19-nortestosterone 12 is prepared from the acetate of 18α-homoestradiol-17β 3 methyl ether, 10.
- Bijoy, Panicker,Ramachandran, Uma,Rao, G. S. R. Subba
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p. 2331 - 2334
(2007/10/02)
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- SYNTHESIS OF SOME EPITESTOSTERONE ANALOGUES
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11β-Hydroxyandrost-4-ene-3,17-dione (III) was converted into a potential metabolite of epitestosterone - 11β,17α-dihydroxyandrost-4-en-3-one (II) in 5 steps, including the inversion of configuration of a 17β-hydroxy group.This inversion was not feasible in the preparation of the analogues X, XIV, XX, and XXII, where the 17α-hydroxy group was introduced first and only then was the rest of molecule modified.
- Chodounska, Hana,Slavikova, Barbora,Kasal, Alexander
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p. 435 - 443
(2007/10/02)
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- REDUCTIVE DESULFONYLATION OF PHENYL SULFONES BY SAMARIUM(II) IODIDE-HEXAMETHYLPHOSPHORIC TRIAMIDE
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Samarium(II) iodide in tetrahydrofuran reductively desulfonylates phenyl sulfones in the presence of hexamethylphosphoric triamide.This transformation is illustrated here for ten substrates, which include secondary alicyclic, β-hydroxy, vicinal bis-, and α,β-unsaturated sulfones.
- Kuenzer, H.,Stahnke, M.,Sauer, G.,Wiechert, R.
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p. 1949 - 1952
(2007/10/02)
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- CYCLIC HYDROCARBONS WITH AN AMINOALKYL SIDECHAIN
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Provided are cyclic hydrocarbons of Formula I with an aminoalkyl sidechain that are useful for treating phospholipase A2 mediated conditions, diabetes, and obesity.
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- On the Rearrangement Reactions of Pregnanediol Disulfate to Δ13-Steroid, and Its 20-Isomeric Sulfate to D-Homosteroids. (Clinical Analysis on Steroids. XLII)
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17α-Ethyl-17β-methyl-5β-pregn-13-en-3α-ol, a major hydrolysis product of pregnanediol disulfate in 3 N hydrochloric acid at 95 deg C, was shown to be formed via two reaction pathways, a concerted mechanism and a stepwise mechanism involving the C20-carbocation, in an approximate ratio of 75:25.D-Hommoannulation of the isomeric sulfate, 5β-pregnane-3α,20β-diol disulfate, giving 17α-methyl-D-homo-5β-androstane-3α-17αβ-diol as a predominant product under the same hydrolysis conditions, was shown to occur mainly (ca. 90percent) by the concerted mechanism.Keywords - pregnanediol disulfate; 5β-pregnane-3α,20β-diol disulfate; hydrolysis; D-homosteroid; steroidal carbocation; Δ13-steroid; rearrangement reaction
- Itoh, Shinji,Ichikawa, Harumi,Takagi, Hidetoshi,Yoshizawa, Itsuo
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p. 4261 - 4268
(2007/10/02)
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- Selective Cathodic Birch Reductions
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The electroreduction of some difficult to reduce substrates was investigated by using aqueous tetrahydrofuran, tetrabutylammonium (TBA+) electrolyte, and mercury cathodes.The reduction products formed in high yields and the current efficiencies were good.Benzene, anisole, 1,2,3,4-tetrahydro-6-methoxynaphthalene and β-estradiol 3-methyl ether reactions were carried out with constant current at room temperature and were found to be more selective than the corresponding alkali metal-ammonia reductions.Selective reduction of the carbonyl function of estrone methyl ether was achieved while the aromatic ring remained intact.The aqueous THF medium did not affect base-sensitive molecules and a reduction product from 17-α-ethynylestradiol 3-methyl ether could be obtained without loss of the ethynyl group.Most of the compounds studied did not exhibit polarographic waves.A reduction product of TBA+ was observed by cyclic voltammetry and it is proposed that TBA "amalgam" may participate as a mediator in the reduction of the organic substrates.
- Kariv-Miller, Essie,Swenson, Karl E.,Lehman, Gaye K.,Andruzzi, Romano
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p. 556 - 560
(2007/10/02)
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- SELECTIVE DEMETHYLATION OF ALIPHATIC METHYL ETHER IN THE PRESENCE OF AROMATIC METHYL ETHER WITH THE ALUMINUM CHLORIDE-SODIUM IODIDE-ACETONITRILE SYSTEM
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A combination system of aluminum chloride-sodium iodide-acetonitrile effects selective demethylation of aliphatic methyl ethers in the presence of aromatic methyl ether.KEYWORDS - demethylation; methyl ether; aluminum chloride; sodium iodide; hard acid; soft nucleophile
- Node, Manabu,Ohta, Keiichiro,Kajimoto, Tetsuya,Nishide, Kiyoharu,Fujita, Eiichi,Fuji, Kaoru
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p. 4178 - 4180
(2007/10/02)
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- Reduction of Steroid 17-Ketones by Enantiomeric Chiral Reducing Agents
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The reduction of steroid 17-ketones by a chiral hydrosilane-rhodium-(-)(2S,3S)-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane reagent allows greater stereoselectivity of 17α-alcohol formation than is obtained by other methods.
- Goendoes, Gyoergy,Orr, James C.
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p. 1238 - 1239
(2007/10/02)
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- Stereoselective and Regioselective Reduction of Steroid Ketones by Potassium Tri(R,S)-s-butyl)borohydride
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Potassium tri(R,S-s-butyl)borohydride reduces 3-oxo-steroids of the 5α- and 5β-series to the axial alcohol under conditions in which the 17- and 20-ketone groups remain unaffected.
- Goendoes, Gyoergy,Orr, James C.
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p. 1239 - 1240
(2007/10/02)
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- Silicon in Synthesis. 10. The (Trimethylisilyl)allyl Anion: A β-Acyl Equivalent for the Conversion of Aldehydes and Ketones into γ-Lactones
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The (trimethylsilyl)allyl anion reacts with a number of ketones and aldehydes to give adducts 11-21, resulting from the γ mode of ambident reactivity.These adducts were epoxidized to provide the corresponding α,β-epoxysilanes 23-31.Treatment of the epoxysilanes with methanol in the presence of boron trifluoride etherate gave the lactol methyl ethers 32-39.Jones oxidation of the lactol methyl ethers gave γ lactones 40-45.Addition of bromine to the 4-hydroxy vinylsilane derivative 19 gave oxetane 47 which was converted into the compounds 49, 50, and 51.Application of the (trimethylsilyl)allyl anion, as its zinc counterion, to the synthesis of 17-spirosteroidal lactones is described.
- Ehlinger, Ed,Magnus, Philip
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p. 5004 - 5011
(2007/10/02)
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