3769-42-4Relevant academic research and scientific papers
Synthesis and biochemical evaluation of lid-open D-amino acid oxidase inhibitors
Szilágyi, Bence,Hargitai, Csilla,Kelemen, ádám A.,Rácz, Anita,Ferenczy, Gy?rgy G.,Volk, Balázs,Keser?, Gy?rgy M.
supporting information, (2019/01/31)
Most of the known inhibitors of D-amino acid oxidase (DAAO) are small polar molecules recognized by the active site of the enzyme. More recently a new class of DAAO inhibitors has been disclosed that interacts with loop 218?224 at the top of the binding pocket. These compounds have a significantly larger size and more beneficial physicochemical properties than most reported DAAO inhibitors, however, their structure-activity relationship is poorly explored. Here we report the synthesis and evaluation of this type of DAAO inhibitors that open the lid over the active site of DAAO. In order to collect relevant SAR data we varied two distinct parts of the inhibitors. A systematic variation of the pendant aromatic substituents according to the Topliss scheme resulted in DAAO inhibitors with low nanomolar activity. The activity showed low sensitivity to the substituents investigated. The variation of the linker connecting the pendant aromatic moiety and the acidic headgroup revealed that the interactions of the linker with the enzyme were crucial for achieving significant inhibitory activity. Structures and activities were analyzed based on available X-ray structures of the complexes. Our findings might support the design of drug-like DAAO inhibitors with advantageous physicochemical properties and ADME profile.
Ruthenium-Catalyzed Dehydrogenative Decarbonylation of Primary Alcohols
Mazziotta, Andrea,Madsen, Robert
, p. 5417 - 5420 (2017/10/06)
Dehydrogenative decarbonylation of a primary alcohol involves the release of both dihydrogen and carbon monoxide to afford the by one carbon unit shorter product. The transformation has now been achieved with a ruthenium-catalyzed protocol by using the complex Ru(COD)Cl2 and the hindered monodentate ligand P(o-tolyl)3 in refluxing p-cymene. The reaction can be applied to both benzylic and long-chain linear aliphatic alcohols. The intermediate aldehyde can be observed during the transformation, which is therefore believed to proceed through two separate catalytic cycles involving first dehydrogenation of the alcohol and then decarbonylation of the resulting aldehyde.
Synthesis of phenyl-1-benzoxepinols isolated from butcher's broom and analogous benzoxepines
Herrmann, Josef M.,Untergehrer, Monika,Juergenliemk, Guido,Heilmann, Joerg,Koenig, Burkhard
supporting information, p. 3170 - 3181 (2014/06/09)
Extracts of Ruscus aculeatus L., known as butcher's broom, are mainly used for the treatment of chronic venous insufficiency (CVI). In a recent study on the phenolic compounds of Rusci rhizoma, new phenyl-1-benzoxepinols were isolated. As the therapeutic effect of butcher's broom is ascribed to the pharmacological activity of the main constituents, steroidal saponins and their aglycones the ruscogenins, the role of the newly identified compounds was of interest. Owing to the low availability of the compounds by isolation, we synthesized them for pharmacological testing. In an ORAC-fluorescein assay they revealed a significant antioxidative activity, which may contribute to the anti-inflammatory properties of the phenolic fraction obtained from Rusci rhizoma extracts. Copyright
Organic super-electron-donors: Initiators in transition metal-free haloarene-arene coupling
Zhou, Shengze,Anderson, Greg M.,Mondal, Bhaskar,Doni, Eswararao,Ironmonger, Vicki,Kranz, Michael,Tuttle, Tell,Murphy, John A.
, p. 476 - 482 (2014/01/17)
Recent papers report transition metal-free couplings of haloarenes to arenes to form biaryls, triggered by alkali metal tert-butoxides in the presence of various additives. These reactions proceed through radical intermediates, but understanding the origin of the radicals has been problematic. Electron transfer from a complex formed from potassium tert-butoxide with additives, such as phenanthroline, has been suggested to initiate the radical process. However, our computational results encouraged us to search for alternatives. We report that heterocycle-derived organic electron donors achieve the coupling reactions and these donors can form in situ in the above cases. We show that an electron transfer route can operate either with phenanthrolines as additives or using pyridine as solvent, and we propose new heterocyclic structures for the respective electron donors involved in these cases. In the absence of additives, the coupling reactions are still successful, although more sluggish, and in those cases benzynes are proposed to play crucial roles in the initiation process.
Iridium-catalyzed dehydrogenative decarbonylation of primary alcohols with the liberation of syngas
Olsen, Esben P. K.,Madsen, Robert
supporting information, p. 16023 - 16029 (2013/02/22)
A new iridium-catalyzed reaction in which molecular hydrogen and carbon monoxide are cleaved from primary alcohols in the absence of any stoichiometric additives has been developed. The dehydrogenative decarbonylation was achieved with a catalyst generated in situ from [Ir(coe)2Cl]2 (coe=cyclooctene) and racemic 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (rac-BINAP) in a mesitylene solution saturated with water. A catalytic amount of lithium chloride was also added to improve the catalyst turnover. The reaction has been applied to a variety of primary alcohols and gives rise to products in good to excellent yields. Ethers, esters, imides, and aryl halides are stable under the reaction conditions, whereas olefins are partially saturated. The reaction is believed to proceed by two consecutive organometallic transformations that are catalyzed by the same iridium(I)-BINAP species. First, dehydrogenation of the primary alcohol to the corresponding aldehyde takes place, which is then followed by decarbonylation to the product with one less carbon atom.
Water accessibility to the binding cleft as a major switching factor from entropy-driven to enthalpy-driven binding of an alkyl group by synthetic receptors
Matsumoto, Sayaka,Iwamoto, Hiroya,Mizutani, Tadashi
supporting information; experimental part, p. 1163 - 1170 (2011/07/07)
Free energy, enthalpy, and entropy changes in the binding of alkyl pyridines to water-soluble zinc porphyrin receptors with varying accessibility of water to the binding cleft were determined to explain why the driving force of hydrophobic effects is enthalp-ic in some occasions and entropic in others. Zinc porphyrins bearing four alkyl pillars with terminal solubilizing poly(oxyethylene) (POE) chains of molecular weight of 750 (1), with eight alkyl pillars with terminal solubilizing POE chains of molecular weight of 350 (3), and with eight alkyl pillars with POE of molecular weight of 750 (4) had a binding cleft with decreasing water accessibility in this order as revealed by binding selectivity of imidazole/pyridine. Although all these porphyrins showed that the free energy of binding (-ΔG°) increases linearly as the alkyl group of the guest is lengthened (-ΔG° per CH2 was 2.6, 2.8, and 2.6kJmol-1 for 1, 3, and 4, respectively), the origin of the free energy gain was much different. Receptor 1 with the most hydrophilic binding site bound the alkyl group by an enthalpic driving force (4-pentylpyridine favored over 4-methylpyridine by ΔΔH° = -16.4 kJmol-1), while receptor 4 with the most hydrophobic binding site by an entropic driving force (4-pentylpyridine favored over 4-methylpyridine by ΔΔ5° = 39.6 JK-1mol-1). Receptor 3 showed intermediate behavior: both enthalpic and entropic terms drove the binding of the alkyl group with the en-thalpic driving force being dominant. The binding site of the four-pillared receptor (1) is open and accessible to water molecules, and is more hydro-philic than that of the eight-pillared receptor (4). We propose that the alkyl chains of 1 are exposed to water to produce a room to accommodate the guest to result in enthalpy-driven hy-drophobic binding, whereas 4 can accommodate the guest without such structural changes to lead to entropy-driven hydrophobic binding. Therefore, accessibility of water or exposure of the binding site to the water phase switches the driving force of hydropho-bic effects from an entropic force to an enthalpic force. 2010 Wiley-VCH Verlag GmbH Co. KGaA, Weinheim.
Acidic rearrangement of (benzyloxy)chalcones: A short synthesis of chamanetin
Sagrera, Gabriel,Seoane, Gustavo
experimental part, p. 4190 - 4202 (2011/03/20)
Treatment of (benzyloxy)chalcones with trifluoroacetic acid in refluxing chloroform gave several new benzyl(hydroxy)flavanones in high yields and good regioselectivities. By using this procedure, we prepared the natural compound chamanetin in good yield from readily available reagents. Georg Thieme Verlag Stuttgart - New York.
Two step synthesis of C2 symmetric 2,6,diarylalkyloxybenzaldehydes - A mitsunobu approach
Smith, John R. Lindsay,O'Brien, Peter,Reginato, Gloriana
, p. 3415 - 3420 (2007/10/03)
A simple two step method for the synthesis of three novel C2 symmetric 2,6-diarylalkyloxybenzaldehydes is described. Starting from resorcinol, the route involves double Mitsunobu reaction with chiral alcohols followed by regiospecific lithiation and formylation.
