28247-15-6Relevant academic research and scientific papers
Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class i HDAC Enzymes and Cancer Cell Proliferation
Tng, Jiahui,Lim, Junxian,Wu, Kai-Chen,Lucke, Andrew J.,Xu, Weijun,Reid, Robert C.,Fairlie, David P.
supporting information, p. 5956 - 5971 (2020/06/05)
AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC50 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86 was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Molecular modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.
Enantioselective biocatalytic reduction of 2,2-disubstituted ethylacetoacetates: An indirect desymmetrization approach for the synthesis of enantiopure (S)-4-hydroxy-3,3-disubstituted pentane-2-ones
Halder, Joydev,Das, Debabrata,Nanda, Samik
, p. 1197 - 1208 (2015/10/28)
Ethyl 2,2-disubstituted-3-oxobutanoates were biocatalytically reduced to the corresponding (S)-ethyl 3-hydroxy-2,2-disubstitutedbutanoate with the growing cells of Klebsiella pneumoniae (NBRC 3319) with excellent enantioselection. The biocatalytically derived enantiopure hydroxyl esters were then synthetically manipulated to give (S)-4-hydroxy-3,3-disubstituted pentane-2-ones. The whole process can be regarded as an indirect enantioselective enzymatic desymmetrization method for the synthesis of (S)-4-hydroxy-3,3-disubstituted pentane-2-ones.
An unexpected directing effect in the asymmetric transfer hydrogenation of α,α-disubstituted ketones
Soni, Rina,Collinson, John-Michael,Clarkson, Guy C.,Wills, Martin
supporting information; experimental part, p. 4304 - 4307 (2011/10/11)
α,α-Disubstituted ketones containing an aromatic ring or alkene are reduced in high enantiomeric excess using an asymmetric transfer hydrogenation catalyst. The sense of reduction indicates that the unsaturated region of the ketone adopts a position adjacent to the Ru-bound η6-arene ring in the reduction transition state.
Synthesis of enantiomerically enriched α,α-disubstituted β,γ-epoxy esters using hydrolytic kinetic resolution catalyzed by salenCo(III)
Viera, Ignacio,Manta, Eduardo,Gonzalez, Lucia,Mahler, Graciela
experimental part, p. 631 - 635 (2010/08/03)
Novel α,α-disubstituted epoxy esters were prepared in enantiopure form by hydrolytic kinetic resolution (HKR) of the corresponding racemic mixtures using chiral salenCo(III) as catalyst. The methodology provides a convenient route to enantioenriched β,γ-epoxy esters 2a, 2c and 2d.
Imidazolium salts as phase transfer catalysts for the dialkylation and cycloalkylation of active methylene compounds
Muthusamy, Sengodagounder,Gnanaprakasam, Boopathy
, p. 635 - 638 (2007/10/03)
The efficient synthesis of 1,1-disubstituted derivatives and the construction of cyclopropane and cyclopentane ring systems via dialkylation and cycloalkylation reactions of active methylene compounds using imidazolium salts as phase transfer catalyst is described. The dialkylation and cycloalkylation reactions of active methylene compounds in the presence of readily available imidazolium salts (ionic liquids) as phase transfer catalysts were performed to afford the respective dialkylated or cycloalkylated products. This method is very efficient for the synthesis of 1,1-disubstituted derivatives and cyclopropane and cyclopentane ring systems in a facile manner.
Synthesis of spiro[5.4]decenones and their transformation into bicyclo[4.4]deca-1,4-dien-3-ones by domino "elimination-double-Wagner- Meerwein-rearrangement" reactions
Bose, Gopal,Ullah, Ehsan,Langer, Peter
, p. 6015 - 6028 (2007/10/03)
The [3+3] cyclization of 1,3-bis-silyl enol ethers with 1,1-diacylcyclopentanes allows a convenient synthesis of spiro[5.4]decenones. Treatment of these compounds with trifluoroacetic acid (TFA) afforded a great variety of bicyclo[4.4.0]deca-1,4-dien-3-on
4-methylene-1,3-dioxolanes having functional groups
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, (2008/06/13)
Novel 4-methylene-1,3-dioxolanes of the general formula I in which R1 denotes hydrogen or alkyl, X denotes a single bond, C1-C18alkylene, cycloalkylene, arylalkylene, —CH2(OCH2CH2)n— or —CH2(OCH(CH3)CH2)n—, in which n is an integer from 1 to 100, and Z means a functional group selected from among —OH, —COOR′ or —OCOR′, in which R′ denotes hydrogen or C1-C8alkyl, are described, as are a process for the production thereof and the intermediates used in this process.
A novel oxidative intramolecular [4+2]cycloaddition of silylene-protected dihydroxystyrene derivatives leading to peri-hydroxy polyclic aromatic compounds: A synthesis of the ABCD ring system of fredericamycin A
Kita,Okunaka,Honda,Kondo,Tamura,Tamura
, p. 2106 - 2114 (2007/10/02)
Heating of the silylene protected dihydroxystyrene generated from the o-hydroxyacetophenone (3a) at 130-150°C for 15-48 h in a sealed tube gave intramolecular [4+2]cycloaddition products (5 and 6). The addition of chloranil to the reaction mixture brought
SYNTHESIS OF CYCLOPENTANE DERIVATIVES IN THE CATHODIC ELECTROLYSIS OF COMPOUNDS WITH AN ACTIVATED METHYLENE GROUP IN THE PRESENCE OF 1,4-DIBROMOBUTANE
Tatarinova, V. I.,Vasil'ev, A. A.,Petrosyan, V. A.
, p. 2399 - 2401 (2007/10/02)
The cathodic electrolysis of compounds with an activated methylene group in the presence of 1,4-dibromobutane leads to 1,1-disubstituted cyclopentanes.
