14772-99-7Relevant academic research and scientific papers
Site-selective oxidation, amination and epimerization reactions of complex polyols enabled by transfer hydrogenation
Hill, Christopher K.,Hartwig, John F.
, p. 1213 - 1221 (2017/11/28)
Polyoxygenated hydrocarbons that bear one or more hydroxyl groups comprise a large set of natural and synthetic compounds, often with potent biological activity. In synthetic chemistry, alcohols are important precursors to carbonyl groups, which then can be converted into a wide range of oxygen- or nitrogen-based functionality. Therefore, the selective conversion of a single hydroxyl group in natural products into a ketone would enable the selective introduction of unnatural functionality. However, the methods known to convert a simple alcohol, or even an alcohol in a molecule that contains multiple protected functional groups, are not suitable for selective reactions of complex polyol structures. We present a new ruthenium catalyst with a unique efficacy for the selective oxidation of a single hydroxyl group among many in unprotected polyol natural products. This oxidation enables the introduction of nitrogen-based functional groups into such structures that lack nitrogen atoms and enables a selective alcohol epimerization by stepwise or reversible oxidation and reduction.
ROR gamma modulators
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Page/Page column 33, (2017/10/25)
The present invention relates to compounds of formula I, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention, suppression or amelioration of a disease mediated by the ROR gamma receptor in a subject in need thereof, in particular diabetes and diabetes-related disorders, specifically type II diabetes, methods of their production, as well as methods of treatment or prevention of such diseases.
Radical-mediated dehydrogenation of bile acids by means of hydrogen atom transfer to triplet carbonyls
Miro,Marin,Miranda
supporting information, p. 2679 - 2683 (2016/03/05)
The aim of the present paper is to explore the potential of radical-mediated dehydrogenation of bile salts (BSs), which is reminiscent of the enzymatic action of hydroxysteroid dehydrogenase enzymes (HSDH). The concept has been demonstrated using triplet carbonyls that can be efficiently generated upon selective UVA-excitation. Hydrogen atom transfer (HAT) from BSs to triplet benzophenone (BP) derivatives gave rise to radicals, ultimately leading to reduction of the BP chromophore with concomitant formation of the oxo-analogs of the corresponding BSs. The direct reactivity of triplet BP with BSs in the initial step was evaluated by determining the kinetic rate constants using laser flash photolysis (LFP). The BP triplet decay was monitored (λmax = 520 nm) upon addition of increasing BS concentrations, and the obtained rate constant values indicated a reactivity of the methine hydrogen atoms in the order of C-3 2 than under O2, also supporting the role of the oxygen-quenchable triplet in the dehydrogenation process. Furthermore, irradiation of deaerated aqueous solutions of sodium cholate in the presence of KPMe provided the oxo-analogs, 3[O],7[O]-CA, 3[O]-CA and 7[O]-CA, arising from the HAT process.
Synthesis of new steroidal inhibitors of P-glycoprotein-mediated multidrug resistance and biological evaluation on K562/R7 erythroleukemia cells
De Ravel, Marc Rolland,Alameh, Ghina,Melikian, Maxime,Mahiout, Zahia,Emptoz-Bonneton, Agnès,Matera, Eva-Laure,Lomberget, Thierry,Barret, Roland,Rocheblave, Luc,Walchshofer, Nadia,Beltran, Sonia,El Jawad, Lucienne,Mappus, Elisabeth,Grenot, Catherine,Pugeat, Michel,Dumontet, Charles,Le Borgne, Marc,Cuilleron, Claude Yves
supporting information, p. 1832 - 1845 (2015/04/21)
A simple route for improving the potency of progesterone as a modulator of P-gp-mediated multidrug resistance was established by esterification or etherification of hydroxylated 5α/β-pregnane-3,20-dione or 5β-cholan-3-one precursors. X-ray crystallography of representative 7α-, 11α-, and 17α-(2′R/S)-O-tetrahydropyranyl ether diastereoisomers revealed different combinations of axial-equatorial configurations of the anomeric oxygen. Substantial stimulation of accumulation and chemosensitization was observed on K562/R7 erythroleukemia cells resistant to doxorubicin, especially using 7α,11α-O-disubstituted derivatives of 5α/β-pregnane-3,20-dione, among which the 5β-H-7α-benzoyloxy-11α-(2′R)-O-tetrahydropyranyl ether 22a revealed promising properties (accumulation index 2.9, IC50 0.5 μM versus 1.2 and 10.6 μM for progesterone), slightly overcoming those of verapamil and cyclosporin A. Several 7α,12α-O-disubstituted derivatives of 5β-cholan-3-one proved even more active, especially the 7α-O-methoxymethyl-12α-benzoate 56 (accumulation index 3.8, IC50 0.2 μM). The panel of modulating effects from different O-substitutions at a same position suggests a structural influence of the substituent completing a simple protection against stimulating effects of hydroxyl groups on P-gp-mediated transport.
ROR GAMMA MODULATORS
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Page/Page column 45, (2013/04/10)
The present invention relates to compounds of formula I, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention, suppression or amelioration of a disease mediated by the ROR gamma receptor in a subject in need thereof, in particular diabetes and diabetes- related disorders, specifically type II diabetes, methods of their production, as well as methods of treatment or prevention of such diseases.
A stereoselective synthesis of the allo-bile acids from the 5β-isomers
Li, Qingjiang,Tochtrop, Gregory P.
supporting information; experimental part, p. 4137 - 4139 (2011/09/19)
The allo-bile acids are a subset of the family of steroidal detergents found in most vertebrates. Because there are no major biological feedstocks for isolation of the allo-bile acids, they must be synthesized from the abundant 5β-reduced isomers. Here we report a general set of methods for the synthesis of allo-bile acids from the corresponding 5-β isomers demarcated by a selective C-3 oxidation, IBX unsaturation, and stereoselective saturation.
NEW STEROID INHIBITORS OF PGP FOR USE FOR INHIBITING MULTIDRUG RESISTANCE
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Page/Page column 47-48, (2011/07/07)
The present invention relates to a compound of formula (I) for its use for reversing or inhibiting multidrug resistance.
Synthesis of heterosteroids. First synthesis of oxa steroid from cholic acid
Ibrahim-Ouali, Malika,Botsi-Nkomendi, Nicaise,Rocheblave, Luc
scheme or table, p. 93 - 95 (2010/03/03)
We wish to report here a new and efficient partial synthesis of 3-oxa-5β-steroid, the first oxa steroid synthesized from cholic acid.
First synthesis of thia steroids from cholic acid
Ibrahim-Ouali, Malika,Rocheblave, Luc
experimental part, p. 701 - 709 (2010/09/03)
Heterosteroids remain interesting due to their potential biological activities. This prompted us to synthesize novel thia steroids possessing the heteroatom in the A-ring. We set out to describe a new and versatile method for preparing 3-thia steroids from cholic acid via a selective oxidation of one hydroxyl group, a BaeyerVilliger oxidation and a photolysis as the key steps. The characteristic 1H and 13C NMR spectroscopic features of the synthesized compounds are reported.
Design and synthesis of bile acid-based amino sterols as antimicrobial agents
Aher, Nilkanth G.,Pore, Vandana S.,Mishra, Nripendra N.,Shukla, Praveen K.,Gonnade, Rajesh G.
supporting information; experimental part, p. 5411 - 5414 (2010/06/16)
New bile acid-based amino sterols were synthesized in good yields from C-3β-oxiranes as key intermediates. These derivatives were evaluated for their in vitro antimicrobial properties against human pathogens. These compounds showed better antibacterial activity as compared to antifungal activity. Compounds 21 and 22 showed comparable antibacterial activity to gentamicin against Staphylococcus aureus with IC50 values of 5.14 and 4.46 μg/mL. This is the first report for the synthesis of C-3β-oxiranes on the steroids having A/B cis ring junction and these oxiranes have been used for the synthesis of amino sterols 17, 18, 21, and 22.
