- Hydroaminoalkylation of Allenes
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The first examples of early-transition-metal-catalyzed hydroaminoalkylation reactions of allenes are reported. Initial studies performed with secondary aminoallenes led to the identification of a suitable titanium catalyst and revealed that under the reaction conditions, the initially formed hydroaminoalkylation products undergo an unexpected titanium-catalyzed rearrangement to form the thermodynamically more stable allylamines. The assumption that this rearrangement involves a reactive allylic cation intermediate provides a simple explanation of the fact that no successful early-transition-metal-catalyzed hydroaminoalkylations of allenes have previously been reported. As a result of the generation of the corresponding cation, the titanium-catalyzed intermolecular hydroaminoalkylation of propa-1,2-diene unexpectedly gives an aminocyclopentane product formed by incorporation of two equivalents of propa-1,2-diene.
- Bielefeld, Jens,Mannhaupt, Steffen,Schmidtmann, Marc,Doye, Sven
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supporting information
p. 967 - 971
(2019/05/10)
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- TRIAZOLE DERIVATIVES AS P2Y14 RECEPTOR ANTAGONISTS
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Described are compounds, which are antagonists of the P2Y14 receptor, for example, a compound of formula (I) in which ring A, R1,R2, R3, and n are as described herein. Also provided are dendron conjugates comprising the compounds, and methods of using the compounds, including a method of treating a disorder, such as inflammation, diabetes, insulin resistance, hyperglycemia, a lipid disorder, obesity, a condition associated with metabolic syndrome, and asthma, and a method of antagonizing P214 receptor activity in a cell.
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- Structure-Based Design of 3-(4-Aryl-1H-1,2,3-triazol-1-yl)-Biphenyl Derivatives as P2Y14 Receptor Antagonists
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UDP and UDP-glucose activate the P2Y14 receptor (P2Y14R) to modulate processes related to inflammation, diabetes, and asthma. A computational pipeline suggested alternatives to naphthalene of a previously reported P2Y14R antagonist (3, PPTN) using docking and molecular dynamics simulations on a hP2Y14R homology model based on P2Y12R structures. By reevaluating the binding of 3 to P2Y14R computationally, two alternatives, i.e., alkynyl and triazolyl derivatives, were identified. Improved synthesis of fluorescent antagonist 4 enabled affinity quantification (IC50s, nM) using flow cytometry of P2Y14R-expressing CHO cells. p-F3C-phenyl-triazole 65 (32) was more potent than a corresponding alkyne 11. Thus, additional triazolyl derivatives were prepared, as guided by docking simulations, with nonpolar aryl substituents favored. Although triazoles were less potent than 3 (6), simpler synthesis facilitated further structural optimization. Additionally, relative P2Y14R affinities agreed with predicted binding of alkynyl and triazole analogues. These triazoles, designed through a structure-based approach, can be assessed in disease models.
- Junker, Anna,Balasubramanian, Ramachandran,Ciancetta, Antonella,Uliassi, Elisa,Kiselev, Evgeny,Martiriggiano, Chiara,Trujillo, Kevin,Mtchedlidze, Giorgi,Birdwell, Leah,Brown, Kyle A.,Harden, T. Kendall,Jacobson, Kenneth A.
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p. 6149 - 6168
(2016/07/26)
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- Ni-Catalyzed Divergent Cyclization/Carboxylation of Unactivated Primary and Secondary Alkyl Halides with CO2
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A user-friendly Ni-catalyzed reductive cyclization/carboxylation of unactivated alkyl halides with CO2 is described. The protocol operates under mild conditions with an excellent chemoselectivity profile and a divergent syn/anti selectivity pat
- Wang, Xueqiang,Liu, Yu,Martin, Ruben
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supporting information
p. 6476 - 6479
(2015/06/08)
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- Enantiomerically enriched tris(boronates): Readily accessible conjunctive reagents for asymmetric synthesis
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The catalytic enantioselective diboration of vinyl boronate esters furnishes chiral tris(boronates) in a selective fashion. Subsequent deborylative alkylation occurs in a diastereoselective fashion, both for intermolecular and intramolecular processes.
- Coombs, John R.,Zhang, Liang,Morken, James P.
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supporting information
p. 16140 - 16143
(2015/01/09)
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- Functionalized phosphonated half-cage molecules as ligands for metal complexes
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Phosphonated molecules, featuring a half-cage structure and a N-lateral chain with additional metal coordinating groups were designed as ligands of metal cations. These compounds were synthesized by a Diels-Alder (DA) strategy, using 1-diethoxyphosphoryl-1,3-butadiene and a series of N-substituted maleimides as dienophiles. Two cycloadducts, bearing a terminal primary alcohol and a terminal iodide, respectively, were used as key intermediates for further functionalizations. Metal coordination properties of the ligands equipped with functionalized N-lateral chains were proven by an ESI-HRMS study. The stoichiometry of one selected EuIII complex with a diphosphonated ligand was determined by photoluminescence spectroscopy in emission mode.
- Villemin, Elise,Herent, Marie-France,Marchand-Brynaert, Jacqueline
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supporting information
p. 6165 - 6178
(2013/01/15)
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- Stereocontrolled synthesis of the diene and triene macrolactones of oximidines I and II: Organometallic coupling versus standard macrolactonization
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(matrix presented) Stereocontrolled construction of the 12-membered diene and triene lactones 1, 2, and 3, characteristic of the antitumor agent oximidines I and II, are reported and were based on an intramolecular Castro-Stephens coupling for the construction of a cyclic enyne or dienyne followed by stereoselective reduction of the cyclic alkyne for introduction of the cis-olefin of the targets. A comparison of the effectiveness of this protocol is made with standard macrolactonization.
- Coleman, Robert S.,Garg, Rahul
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p. 3487 - 3490
(2007/10/03)
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- Scope and Mechanism of Stannylalumination of 1-Alkynes
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Terminal acetylenes react with Bu3SnAlEt2 in the presence of Cu+ or Pd0 catalysts to give 1,2-dimetallo-1-alkenes in highly regio- and stereoselective reactions.These intermediates can be selectively functionalized at the vinyl-aluminum bond to provide vinylstannanes, which upon transmetalation and further reaction with electrophiles give stereodefined trisubstituted olefins.In sharp contrast to the normal behavior of alkylaluminum reagents, this process tolerates a number of functional groups including OH, OAc, OTHP, and Br.Mechanistic investigations suggest that the addition of Bu3SnAlEt2 to 1-alkynes proceeds via stannylcupration followed by capture of the stannylcuprate adduct by electrophilic aluminum.
- Sharma, Sunaina,Oehlschlager, Allan C.
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p. 5064 - 5073
(2007/10/02)
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- Synthesis of -Catenanes from -Rotaxanes
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Starting from the rotaxane 18a a mixture of catenane 21 and rotaxane 23 is obtained by attaching a polymethylene bridge between the methylene groups in α-position of the sulfonyl groups.The isocyclic catenane 28 containing a 28- and a 46-membered ring is
- Schill, Gottfried,Schweickert, Norbert,Fritz, Hans,Vetter, Walter
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p. 961 - 970
(2007/10/02)
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