29670-63-1Relevant articles and documents
Enantioselective iridium catalyzed α-alkylation of azlactones by a tandem asymmetric allylic alkylation/aza-Cope rearrangement
Bai, Xue-Dan,Zhang, Qing-Feng,He, Ying
supporting information, p. 5547 - 5550 (2019/05/21)
The development of an iridium catalyzed enantioselective α-alkylation of azlactones has been described. The reaction provides rapid access to a wide range of enantio-enriched quaternary carbon center allylated 2,4-diaryloxazol-5(2H)-ones in excellent yiel
Palladium-Catalyzed Ortho-Alkoxylation of N-Benzoyl α-Amino Acid Derivatives at Room Temperature
Li, Shuangjie,Zhu, Wei,Gao, Feng,Li, Chunpu,Wang, Jiang,Liu, Hong
, p. 126 - 134 (2017/04/26)
An efficient palladium-catalyzed ortho-alkoxylation of N-benzoyl α-amino acid derivatives at room temperature has been explored. This novel transformation, using amino acids as directing groups, Pd(OAc)2 as catalyst, alcohols as the alkoxylation reagents, and PhI(OAc)2 as the oxidant, showed wide generality, good functional tolerance, and high monoselectivity and regioselectivity.
Enantioselective construction of tetrasubstituted stereogenic carbons through bronsted base catalyzed michael reactions: α′-hydroxy enones as key enoate equivalent
Badiola, Eider,Fiser, Bla,Gmez-Bengoa, Enrique,Mielgo, Antonia,Olaizola, Iurre,Urruzuno, Iaki,Garca, Jess M.,Odriozola, Jos M.,Razkin, Jess,Oiarbide, Mikel,Palomo, Claudio
supporting information, p. 17869 - 17881 (2015/02/19)
Catalytic and asymmetric Michael reactions constitute very powerful tools for the construction of new C-C bonds in synthesis, but most of the reports claiming high selectivity are limited to some specific combinations of nucleophile/electrophile compound types, and only few successful methods deal with the generation of all-carbon quaternary stereocenters. A contribution to solve this gap is presented here based on chiral bifunctional Bronsted base (BB) catalysis and the use of α′-oxy enones as enabling Michael acceptors with ambivalent H-bond acceptor/donor character, a yet unreported design element for bidentate enoate equivalents. It is found that the Michael addition of a range of enolizable carbonyl compounds that have previously demonstrated challenging (i.e., α-substituted 2-oxindoles, cyanoesters, oxazolones, thiazolones, and azlactones) to α′-oxy enones can afford the corresponding tetrasubstituted carbon stereocenters in high diastereo- and enantioselectivity in the presence of standard BB catalysts. Experiments show that the α′-oxy ketone moiety plays a key role in the above realizations, as parallel reactions under identical conditions but using the parent α,β-unsaturated ketones or esters instead proceed sluggish and/or with poor stereoselectivity. A series of trivial chemical manipulations of the ketol moiety in adducts can produce the corresponding carboxy, aldehyde, and ketone compounds under very mild conditions, giving access to a variety of enantioenriched densely functionalized building blocks containing a fully substituted carbon stereocenter. A computational investigation to rationalize the mode of substrate activation and the reaction stereochemistry is also provided, and the proposed models are compared with related systems in the literature.
Catalyst-free synthesis of N -(1,7-dioxotetrahydropyrazolo[1,2-a]pyrazol-2- yl)benzamide derivatives by 1,3-dipolar cycloaddition and rearrangement
Liu, Wenjing,Xu, Yu,Sun, Xingxia,Lu, Dapeng,Guo, Lijuan
supporting information, p. 1093 - 1096 (2014/05/20)
N-(1,7-Dioxotetrahydropyrazolo[1,2-a]pyrazol-2-yl)-benzamide derivatives, a novel class of compounds, were synthesized by 1,3-dipolar cycloaddition of azomethine imines with azlactones and subsequent rearrangement. The reaction can be completed rapidly under mild conditions without a catalyst. Georg Thieme Verlag Stuttgart New York.
Synthesis of di- and tri-substituted imidazole-4-carboxylates via PBu3-mediated [3+2] cycloaddition
Hsu, Mei-Yuan,Dietrich, Justin,Hulme, Christopher,Shaw, Arthur Y.
, p. 1538 - 1542 (2013/05/21)
Some new di- and trisubstituted imidazole-4-carboxylates were prepared from amidoacetic acids 3 in the present report. The key step to establish such imidazole- 4-carboxylates stemmed from the PBu3-mediated [3+2] cycloaddition between in situ-generated Δ2-oxazolinone 4 and ethyl cyanoformate6. Our results indicated that trisubstituted imidazoles 7-20 were afforded in better yields than those of disubstituted imidazoles 21-27. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications1 to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
Inhibition of the human proteasome by imidazoline scaffolds
Azevedo, Lauren M.,Lansdell, Theresa A.,Ludwig, Jacob R.,Mosey, Robert A.,Woloch, Daljinder K.,Cogan, Dillon P.,Patten, Gregory P.,Kuszpit, Michael R.,Fisk, Jason S.,Tepe, Jetze J.
, p. 5974 - 5978 (2013/08/23)
The proteasome has emerged as the primary target for the treatment of multiple myeloma. Unfortunately, nearly all patients develop resistance to competitive-type proteasome inhibitors such as bortezomib. Herein, we describe the optimization of noncompetit
One-pot preparation of oxazol-5(4H)-ones from amino acids in aqueous solvents
Fujita, Hikaru,Kunishima, Munetaka
, p. 907 - 912 (2012/08/08)
A method for one-pot synthesis of oxazol-5(4H)-ones has been developed using 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), which is available for the activation of carboxylic acids in an aqueous solvent. The oxazolones were prepared by the TV-acylation of amino acids with carboxylic acids and the subsequent cyclodehydration of the resulting N-acylamino acids by the addition of N,N-diethylaniline. Since both these reactions proceed effectively with the same coupling reagent, DMT-MM, in aqueous solvents, the procedure is simplified and becomes easy to perform. In addition, 5-(triazinyloxy)oxazole derivatives have been synthesized by controlling the basicity of the reaction system.
Application of a novel [3+2] cycloaddition reaction to prepare substituted imidazoles and their use in the design of potent DFG-out allosteric B-Raf inhibitors
Dietrich, Justin,Gokhale, Vijay,Wang, Xiadong,Hurley, Laurence H.,Flynn, Gary A.
experimental part, p. 292 - 304 (2010/04/02)
B-Raf protein kinase, which is a key signaling molecule in the RAS-RAF-MEK-ERK signaling pathway, plays an important role in many cancers. The B-Raf V600E mutation represents the most frequent oncogenic kinase mutation known and is responsible for increas
Structural-activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-κB mediated IL-6 production
Kahlon, Daljinder K.,Lansdell, Theresa A.,Fisk, Jason S.,Tepe, Jetze J.
supporting information; experimental part, p. 3093 - 3103 (2009/10/02)
We herein describe the synthesis and anti-inflammatory properties of a small library of imidazoline-based NF-κB inhibitors. The structure-activity relationship of various substituents on an imidazoline core structure was evaluated for the ability to inhibit NF-κB mediated IL-6 production. Optimization of the scaffolds was pursued by correlating luciferase-based NF-κB reporter assays with inhibition of IL-6 production in IL-1β stimulated human blood. Several derivatives were found to inhibit NF-κB mediated IL-6 production in the nanomolar range in IL-1β stimulated human blood.
Nuclear factor-κB mediated inhibition of cytokine production by imidazoline scaffolds
Kahlon, Daljinder K.,Lansdell, Theresa A.,Fisk, Jason S.,Hupp, Christopher D.,Friebe, Timothy L.,Hovde, Stacy,Jones, A. Daniel,Dyer, Richard D.,Henry, R. William,Tepe, Jetze J.
supporting information; experimental part, p. 1302 - 1309 (2009/12/26)
The mammalian nuclear transcription factor NF-κB is responsible for the transcription of multiple cytokines, including the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Elevated levels of pro-inflammatory cytokines play an important role in the pathogenesis of inflammatory disorders such as rheumatoid arthritis (RA). Inhibition of the pro-inflammatory transcription factor NF-κB has therefore been identified as a possible therapeutic treatment for RA. We describe herein the synthesis and biological activity of a series of imidazoline-based scaffolds as potent inhibitors of NF-κB mediated gene transcription in cell culture as well as inhibitors of TNF-α and IL-6 production in interleukin 1 beta (IL-1β) stimulated human blood.
