1091-93-6Relevant academic research and scientific papers
Birch Reductions of Methoxyaromatics in Aqueous Solution
Swenson, Karl E.,Zemach, Dvora,Nanjundiah, Chenniah,Kariv-Miller, Essie
, p. 1777 - 1779 (1983)
A Birch-like electroreduction of methoxyaromatics in aqueous solutions was achieved, probably through the intermediacy of a tetrabutylammonium amalgam.
Doping in sport-2. Quantification of the impurity 19-norandrostenedione in pharmaceutical preparations of norethisterone
Walker, Christopher J.,Cowan, David A.,James, Vivian H.T.,Lau, Joanne C.Y.,Kicman, Andrew T.
, p. 335 - 340 (2009)
The finding of measurable amounts of 19-norandrostenedione in norethisterone tablets prompted us to develop an assay to quantify this steroid. 19-Norandrostenedione is an anabolic steroid whose use in sport is prohibited by the World Anti-Doping Agency (WADA). The assay was developed using isotope dilution and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of 19-norandrostenedione in norethisterone formulations, with [3,4-13C2]-19-norandrostenedione as the internal standard. The results showed amounts up to 1.01 ± 0.01 μg (mean ± S.E.M.) per tablet in those containing 5 mg of norethisterone or norethisterone acetate (0.02%, w/w) and up to 0.5 ± 0.01 μg (mean ± S.E.M.) per tablet (0.05%, w/w) in oral contraceptive tablets containing 0.35-1.5 mg of norethisterone or norethisterone acetate. No tablet tested exceeded the British Pharmacopoeia limit of 0.1% for this impurity.
Scalable and safe synthetic organic electroreduction inspired by Li-ion battery chemistry
Peters, Byron K.,Rodriguez, Kevin X.,Reisberg, Solomon H.,Beil, Sebastian B.,Kawamata, Yu,Baran, Phil S.,Hickey, David P.,Klunder, Kevin,Gorey, Timothy J.,Anderson, Scott L.,Minteer, Shelley D.,Collins, Michael,Starr, Jeremy,Chen, Longrui,Udyavara, Sagar,Neurock, Matthew
, p. 838 - 845 (2019/04/30)
Reductive electrosynthesis has faced long-standing challenges in applications to complex organic substrates at scale. Here, we show how decades of research in lithium-ion battery materials, electrolytes, and additives can serve as an inspiration for achieving practically scalable reductive electrosynthetic conditions for the Birch reduction. Specifically, we demonstrate that using a sacrificial anode material (magnesium or aluminum), combined with a cheap, nontoxic, and water-soluble proton source (dimethylurea), and an overcharge protectant inspired by battery technology [tris(pyrrolidino)phosphoramide] can allow for multigram-scale synthesis of pharmaceutically relevant building blocks. We show how these conditions have a very high level of functional-group tolerance relative to classical electrochemical and chemical dissolving-metal reductions. Finally, we demonstrate that the same electrochemical conditions can be applied to other dissolving metal-type reductive transformations, including McMurry couplings, reductive ketone deoxygenations, and epoxide openings.
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 (2007/10/03)
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.
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 (2007/10/03)
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.
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 (2007/10/03)
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.
Direct Conversion of 13β-Alkylgonatetraenes into 13β-Alkylgon-4-en-3-ones
Bijoy, Panicker,Ramachandran, Uma,Rao, G. S. R. Subba
, p. 2331 - 2334 (2007/10/02)
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.
Selective Cathodic Birch Reductions
Kariv-Miller, Essie,Swenson, Karl E.,Lehman, Gaye K.,Andruzzi, Romano
, p. 556 - 560 (2007/10/02)
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.
Organophosphorus Redox Systems
Kaim, Wolfgang,Lechner-Knoblauch, Ulrike,Haenel, Peter,Bock, Hans
, p. 4206 - 4208 (2007/10/02)
Redox systems involving R2P-, R2P(X)-, and R3P+ -substituted benzenes and biphenyls have been studied by cyclic voltammetry in dimethylformamide.The first one-electron reduction was found to be reversible in several instances, and stable radical anions, cations and uncharged radicals were detected by high-resolution electron spin resonance.The second reduction step was found to be irreversible in all cases investigated.The electrochemical and spectroscopic data illustrate the considerable difference in acceptor strength between R2P and R3P+ substituents; MO calculations of the radical species give a quantitative measure for this difference and for the overall substituent effects.A comparison is made between the organophosphorus redox systems presentented and the quinone/hydroquinone redox systems.
Cathodic Birch Reduction of Methoxyaromatics and Steroids in Aqueous Solution
Kariv-Miller, Essie,Swenson, Karl E.,Zemach, Dvora
, p. 4210 - 4214 (2007/10/02)
The electroreduction of methoxybenzene, 1,2,3,4-tetrahydro-6-methoxynaphthalene, and several aromatic steroids using aqueous tetrabutylammonium hydroxide solutions is described.The reactions proceed in high yields, and the corresponding dihydro products are formed.Temperature and electrolyte concentration were found to have a strong effect on the reaction rate.A direct electron transfer to the aromatics is unlikely, and a possible reduction mechanism involving the intermediacy of tetrabutylammonium amalgam is proposed.
