13013-02-0Relevant articles and documents
LP99: Discovery and synthesis of the first selective BRD7/9 bromodomain inhibitor
Clark, Peter G. K.,Vieira, Lucas C. C.,Tallant, Cynthia,Fedorov, Oleg,Singleton, Dean C.,Rogers, Catherine M.,Monteiro, Octovia P.,Bennett, James M.,Baronio, Roberta,Müller, Susanne,Daniels, Danette L.,Méndez, Jacqui,Knapp, Stefan,Brennan, Paul E.,Dixon, Darren J.
, p. 6217 - 6221 (2015)
The bromodomain-containing proteins BRD9 and BRD7 are part of the human SWI/SNF chromatin-remodeling complexes BAF and PBAF. To date, no selective inhibitor for BRD7/9 has been reported despite its potential value as a biological tool or as a lead for future therapeutics. The quinolone-fused lactam LP99 is now reported as the first potent and selective inhibitor of the BRD7 and BRD9 bromodomains. Development of LP99 from a fragment hit was expedited through balancing structure-based inhibitor design and biophysical characterization against tractable chemical synthesis: Complexity-building nitro-Mannich/lactamization cascade processes allowed for early structure-activity relationship studies whereas an enantioselective organocatalytic nitro-Mannich reaction enabled the synthesis of the lead scaffold in enantioenriched form and on scale. This epigenetic probe was shown to inhibit the association of BRD7 and BRD9 to acetylated histones invitro and in cells. Moreover, LP99 was used to demonstrate that BRD7/9 plays a role in regulating pro-inflammatory cytokine secretion.
N-heterocyclic carbene catalyzed C-C bond cleavage in redox esterifications of chiral formylcyclopropanes
Sohn, Stephanie S.,Bode, Jeffrey W.
, p. 6021 - 6024 (2006)
(Chemical Equation Presented) A clean break: An N-heterocyclic carbene catalyzes the ring-opening of chiral non-racemic formylcyclopropanes, with simultaneous oxidation of the aldehyde function and without the need for stoichiometric reagents. The activated carboxylate intermediate is trapped by a variety of nucleophiles, thus leading to chiral esters, thioesters, or carboxylic acids (see scheme; DBU = 1,8-diazabicyclo-[5.4.0]undec-7-ene, EWG = electron-withdrawing group, Nu = nucleophile.)
One-step hydrothermal amino-grafting of graphene oxide as an efficient solid base catalyst
Zhang, Yicheng,Chen, Chunlin,Wu, Guangjun,Guan, Naijia,Li, Landong,Zhang, Jian
, p. 4305 - 4308 (2014)
A one-step hydrothermal route is developed to prepare amino-grafted graphene oxide as an environmentally benign heterogeneous solid base catalyst.
Synthesis and antiarrhythmic activity of (1,3-dimethyl-5-nitro-5- hexahydropyrimidinyl)-propionic acid methyl ester
Shakirov,Yarmukhamedov,Vlasova,Baibulatova,Khisamutdinova,Gabdrakhmanova,Karachurina,Baschenko
, p. 29 - 31 (2006)
(1,3-Dimethyl-5-nitro-5-hexahydropyrimidinyl)propionic acid methyl ester (I) was obtained with a 83% yield using a Mannich type reaction of 4-nitrobutanoic acid methyl ester with excess formalin and methylamine. It was found that compound I possesses low toxicity and shows antiarrhythmic activity on models of arrhythmia induced by intravenous injections of calcium chloride and aconitine in rats.
Solvent-Free Henry and Michael Reactions with Nitroalkanes Promoted by Potassium Carbonate as a Versatile Heterogeneous Catalyst
Bosica, Giovanna,Polidano, Kurt
, (2017/07/11)
The use of a simple weak inorganic base such as potassium carbonate facilitated the formation of carbon-carbon bonds through both the Henry and the Michael reactions with nitrocompounds. The application of this catalyst under environmentally friendly solventless heterogeneous conditions gave satisfactory to good yields of β-nitroalcohols, involving aliphatic and aromatic starting materials, as well as high to excellent yields in the formation of Michael adducts using several different Michael acceptors and nitroalkanes.
Oxidative Amidation of Nitroalkanes with Amine Nucleophiles using Molecular Oxygen and Iodine
Li, Jing,Lear, Martin J.,Kawamoto, Yuya,Umemiya, Shigenobu,Wong, Alice R.,Kwon, Eunsang,Sato, Itaru,Hayashi, Yujiro
supporting information, p. 12986 - 12990 (2015/11/02)
The formation of amides and peptides often necessitates powerful yet mild reagent systems. The reagents used, however, are often expensive and highly elaborate. New atom-economical and practical methods that achieve such goals are highly desirable. Ideally, the methods should start with substrates that are readily available in both chiral and non-chiral forms and utilize cheap reagents that are compatible with a wide variety of functional groups, steric encumberance, and epimerizable stereocenters. A direct oxidative method was developed to form amide and peptide bonds between amines and primary nitroalkanes simply by using I2 and K2CO3 under O2. Contrary to expectations, a 1:1 halogen-bonded complex forms between the iodonium source and the amine, which reacts with nitronates to form α-iodo nitroalkanes as precursors to the amides.
Synthesis of functionalized γ-lactone via Sakurai exo -cyclization/rearrangement of 3,3-bis(silyl) enol ester with a tethered acetal
Yin, Zhiping,Liu, Zengjin,Huang, Zhenggang,Chu, Yang,Chu, Zhiwen,Hu, Jia,Gao, Lu,Song, Zhenlei
supporting information, p. 1553 - 1556 (2015/03/30)
An efficient synthesis of functionalized γ-lactones has been developed involving Sakurai exo-cyclization/rearrangement of 3,3-bis(silyl) enol esters with a tethered acetal. While the steric and electronic effects of geminal bis(silane) favor the desired Sakurai pathway, the methoxy species formed in the deprotection step also facilitates both cyclization and rearrangement. The synthetic value of this approach has been demonstrated by efficiently transforming the E-vinylsilane into enyne and the γ-lactone moiety into multisubstituted THF.
Catalytic Asymmetric Synthesis of Isoxazolines from Silyl Nitronates
Han, Xiaoyu,Dong, Li,Geng, Caiwei,Jiao, Peng
supporting information, p. 3194 - 3197 (2015/07/15)
1,3-Dipolar cycloadditions of triisopropylsilyl nitronates and 2-alkylacroleins produced isoxazolines bearing a chiral quaternary center in high yields and enantioselectivities with the aid of a chiral oxazaborolidine catalyst. One chiral isoxazoline product was converted to (R)-(+)-Tanikolide in 9 steps in a total yield of 43%. (Chemical Equation Presented).
Stereoselective aza-Henry reaction of chiral tert-butanesulfinyl imines with methyl or ethyl 4-nitrobutanoate: Easy access to enantioenriched 6-substituted piperidine-2,5-diones
Garca-Muoz, M. Jess,Foubelo, Francisco,Yus, Miguel
, p. 1419 - 1432 (2015/06/02)
The base-catalyzed addition of 4-nitrobutanoates 6 to N-tert-butanesulfinyl imines 8 under solvent-free reaction conditions proceeded with high face diastereoselectivity. The resulting β-nitroamine derivatives 9 were easily transformed into 6-substituted piperidine-2,5-diones 11 upon removal of the sulfinyl group with concomitant δ-lactam formation and functional group transformation under Nef reaction conditions.
Cascade formation of isoxazoles: Facile base-mediated rearrangement of substituted oxetanes
Burkhard, Johannes A.,Tchitchanov, Boris H.,Carreira, Erick M.
supporting information; scheme or table, p. 5379 - 5382 (2011/07/08)
Give me five! Nitro compounds and oxetan-3-one react through an intriguing cascade sequence to give isoxazole-4-carbaldehydes using inexpensive reagents in a one-pot procedure (see scheme; Ms=methanesulfonyl). A variety of 3-substituted isoxazole-4-carbaldehydes were obtained in high overall yields.
