71510-41-3Relevant articles and documents
Gold N-Heterocyclic Carbene Catalysts for the Hydrofluorination of Alkynes Using Hydrofluoric Acid: Reaction Scope, Mechanistic Studies and the Tracking of Elusive Intermediates
Bédard, Sandrine,Cavallo, Luigi,Falivene, Laura,Gauthier, Rapha?l,Nolan, Steven P.,Paquin, Jean-Fran?ois,Saab, Marina,Tzouras, Nikolaos V.,Van Hecke, Kristof,Zhang, Ziyun
supporting information, (2021/12/09)
An efficient and chemoselective methodology deploying gold-N-heterocyclic carbene (NHC) complexes as catalysts in the hydrofluorination of terminal alkynes using aqueous HF has been developed. Mechanistic studies shed light on an in situ generated catalyst, formed by the reaction of Br?nsted basic gold pre-catalysts with HF in water, which exhibits the highest reactivity and chemoselectivity. The catalytic system has a wide alkyl substituted-substrate scope, and stoichiometric as well as catalytic reactions with tailor-designed gold pre-catalysts enable the identification of various gold species involved along the catalytic cycle. Computational studies aid in understanding the chemoselectivity observed through examination of key mechanistic steps for phosphine- and NHC-coordinated gold species bearing the triflate counterion and the elusive key complex bearing a bifluoride counterion.
Electrochemistry Broadens the Scope of Flavin Photocatalysis: Photoelectrocatalytic Oxidation of Unactivated Alcohols
Zhang, Wen,Carpenter, Keith L.,Lin, Song
supporting information, p. 409 - 417 (2019/11/25)
Riboflavin-derived photocatalysts have been extensively studied in the context of alcohol oxidation. However, to date, the scope of this catalytic methodology has been limited to benzyl alcohols. In this work, mechanistic understanding of flavin-catalyzed oxidation reactions, in either the absence or presence of thiourea as a cocatalyst, was obtained. The mechanistic insights enabled development of an electrochemically driven photochemical oxidation of primary and secondary aliphatic alcohols using a pair of flavin and dialkylthiourea catalysts. Electrochemistry makes it possible to avoid using O2 and an oxidant and generating H2O2 as a byproduct, both of which oxidatively degrade thiourea under the reaction conditions. This modification unlocks a new mechanistic pathway in which the oxidation of unactivated alcohols is achieved by thiyl radical mediated hydrogen-atom abstraction.
UR-DEBa242: A Py-5-Labeled Fluorescent Multipurpose Probe for Investigations on the Histamine H3 and H4 Receptors
Bartole, Edith,Gr?tz, Lukas,Littmann, Timo,Wifling, David,Seibel, Ulla,Buschauer, Armin,Bernhardt, Günther
supporting information, p. 5297 - 5311 (2020/06/08)
Comprehensively characterized fluorescent probes for the histamine H3 receptor (H3R) and especially for the H4R orthologs [e.g., human (h) and mouse (m)] are highly needed as versatile complementary tools to radioligands. In view of fluorescent probes for BRET-based binding studies and for localizing the H4R in live cells, we synthesized and biologically characterized Py-5-labeled histamine derivatives. The most notable compound was UR-DEBa242 (26, 1-[4-(1H-Imidazol-4-yl)butyl]-4-{(1E,3E)-4-[4-(dimethylamino)phenyl]buta-1,3-dienyl}-2,6-dimethylpyridinium hydrotrifluoroacetate trifluoroacetate), acting as a partial agonist at the hH3R [pEC50 (reporter gene) 8.77] and as an inverse agonist/antagonist at the h/mH4Rs [pIC50 (reporter gene) 8.76/7.08; pIC50/pKb (β-arrestin2) 7.81/7.30]. In confocal microscopy, 26 proved suitable for hH4R localization and trafficking studies in live cells. BRET-based binding at the NLuc-hH3,4Rs/mH4R [pKd 8.78/7.75/7.18, comparable to binding constants from radioligand binding/flow cytometry; fast association/dissociation (a?2 min)] revealed 26 as a useful molecular tool to determine hH3,4Rs/mH4R binding affinities of ligands binding to these receptors.
Photoinduced, Copper-Catalyzed Decarboxylative C-N Coupling to Generate Protected Amines: An Alternative to the Curtius Rearrangement
Zhao, Wei,Wurz, Ryan P.,Peters, Jonas C.,Fu, Gregory C.
supporting information, p. 12153 - 12156 (2017/09/12)
The Curtius rearrangement is a classic, powerful method for converting carboxylic acids into protected amines, but its widespread use is impeded by safety issues (the need to handle azides). We have developed an alternative to the Curtius rearrangement that employs a copper catalyst in combination with blue-LED irradiation to achieve the decarboxylative coupling of aliphatic carboxylic acid derivatives (specifically, readily available N-hydroxyphthalimide esters) to afford protected amines under mild conditions. This C-N bond-forming process is compatible with a wide array of functional groups, including an alcohol, aldehyde, epoxide, indole, nitroalkane, and sulfide. Control reactions and mechanistic studies are consistent with the hypothesis that copper species are engaged in both the photochemistry and the key bond-forming step, which occurs through out-of-cage coupling of an alkyl radical.
Cobaloxime-catalyzed hydration of terminal alkynes without acidic promoters
Hou, Shengtai,Yang, Hongjian,Cheng, Bin,Zhai, Hongbin,Li, Yun
, p. 6926 - 6929 (2017/07/10)
Cobaloxime (Co(dmgBF2)2·2H2O), an inexpensive first-row transition-metal complex, catalyzed hydration of terminal alkynes gave the corresponding methyl ketones in good to excellent yields under neutral conditions (additional protic acids and silver salts are not required). A wide range of functional groups, such as allyl ether, benzyl ethers, carboxylic esters, imides, amides, nitro, and halogens, were tolerated. The mild reaction conditions together with the inexpensive feature and easy availability of the catalyst well address the current challenges in the field of alkyne hydration.
Synthesis and functional characterization of imbutamine analogs as histamine H3 and H4 receptor ligands
Geyer, Roland,Kaske, Melanie,Baumeister, Paul,Buschauer, Armin
, p. 77 - 88 (2014/03/21)
Imbutamine (4-(1H-imidazol-4-yl)butanamine) is a potent histamine H 3 (H3R) and H4 receptor (H4R) agonist (EC50 values: 3 and 66 nM, respectively). Aiming at improved selectivity for the H4R, the imidazole ring in imbutamine was methyl-substituted or replaced by various differently substituted heterocycles (1,2,3-triazoles, 1,2,4-triazoles, pyridines, pyrimidines) as potential bioisosteres. Investigations in [35S]GTPγS binding assays using membranes of Sf9 insect cells expressing the respective human histamine receptor subtype revealed only very weak activity of most of the synthesized hetarylalkylamines at both receptors. By contrast, the introduction of substituents at the 4-imidazolyl ring was most effective regarding H 4R selectivity. This holds for methyl substitution in position 2 and, especially, in position 5. 5-Methylimbutamine (H4R: EC50 = 59 nM, α = 0.8) was equipotent with imbutamine at the hH4R, but revealed about 16-fold selectivity for the hH4R compared to the hH3R (EC50 980 nM, α = 0.36), whereas imbutamine preferred the hH3R. The functional activities were in agreement with radioligand binding data. The results support the hypothesis that, by analogy with histamine, methyl substitution in histamine homologs offers a way to shift the selectivity in favor of the H4R. According to a bioisosteric approach, the imidazole ring in the dual histamine H3/H4 receptor agonist imbutamine (n = 4) was replaced by various five- and six-membered N-heterocycles. Whereas these structural modifications resulted in a reduction or loss of activity at both receptors, 5-methyl substitution at the imidazol-4-yl ring in imbutamine changed the receptor subtype selectivity in favor of the H4R.
Mild chemo-selective hydration of terminal alkynes catalysed by AgSbF 6
Thuong, Mathieu Bui The,Mann, Andre,Wagner, Alain
supporting information; experimental part, p. 434 - 436 (2012/01/05)
The chemo-selective hydration of a wide range of non-activated terminal alkynes catalysed by AgSbF6 under mild conditions is reported.
Synthesis and structure-activity relationships of cyanoguanidine-type and structurally related histamine H4 receptor agonists
Igel, Patrick,Geyer, Roland,Strasser, Andrea,Dove, Stefan,Seifert, Roland,Buschauer, Armin
supporting information; experimental part, p. 6297 - 6313 (2010/03/24)
Recently, we identified high-affinity human histamine H3 (hH3R) and H4 receptor (hH4R) ligands among a series of NG-acylated imidazolylpropylguanidines, which were originally designed as histamine H2 receptor (H2R) agonists. Aiming at selectivity for hH4R, the acylguanidine group was replaced with related moieties. Within a series of cyanoguanidines, 2-cyano-1-[4-(1H-imidazol-4-yl)butyl]-3-[(2-phenylthio)ethyl]guanidine (UR-PI376, 67) was identified as the most potent hH4R agonist (pEC50=7.47, α=0.93) showing negligible hH1R and hH2R activities and significant selectivity over the hH3R (pKB=6.00, α=-0.28), as determined in steady-state GTPase assays using membrane preparations of hHxR-expressing Sf9 cells. In contrast to previously described selective H4R agonists, this compound and other 3-substituted derivatives are devoid of agonistic activity at the other HR subtypes. Modeling of the binding mode of 67 suggests that the cyanoguanidine moiety forms chargeassisted hydrogen bonds not only with the conserved Asp-94 but also with the hH4R-specific Arg-341 residue. 2-Carbamoyl-1-[2-(1H-imidazol-4-yl)ethyl]-3-(3-phenylpropyl)guanidine (UR-PI97, 88) was unexpectedly identified as a highly potent and selective hH3R inverse agonist (pKB=8.42, >300-fold selectivity over the other HR subtypes). 2009 American Chemical Society.
Cis- and trans-strapped calix[4]pyrroles bearing phthalamide linkers: Synthesis and anion-binding properties
Lee, Chang-Hee,Lee, Jin-Suk,Na, Hee-Kyung,Yoon, Dae-Wi,Miyaji, Hidekazu,Cho, Won-Seob,Sessler, Jonathan L.
, p. 2067 - 2074 (2007/10/03)
(Chemical Equation Presented) New cis-strapped calix[4] pyrrole derivatives 12, 13, and 19 and trans-strapped systems 14 and 15 bearing isophthalate-derived diamide spacers linked to the tetrapyrrolic core have been synthesized and characterized by spectr
