615-13-4Relevant articles and documents
2-Indanone and Its Enol. The Effect of a Conjugated Phenyl Group on Enol and Enolate Stability
Keeffe, J.R.,Kresge, A.J.,Yin, Y.
, p. 8201 - 8206 (1988)
Rate and equilibrium constants for the interconversion of 2-indanone with its enol and enolate ion have been determined in dilute aqueous acid and base solution (ionic strength=0.10 M) at 25 deg C.These measurements provide the keto-enol equilibrium constant, pKE=3.84+-0.04; the acidity constant of the ketone ionizing as a carbon acid, pKaK=12.20+-0.08; and the acidity constant of the enol ionizing as an oxygen acid, pKaE=8.36+-0.09.Comparison of these results with values for acetone show that the effects of the benzene ring are large: a factor of 1E4.4 on KE, 1E7.0 on KaK, and 1E2.6 on KaE.Considerably smaller phenyl effects are estimated for the acyclic model ketone phenylacetone; reduced coplanarity in the latter is suggested as the major reason for the reduced effects.In terms of rate constants,the greater enol content of 2-indanone relative to acetone manifests itself in the acid-catalyzed reaction mainly as a largely reduced rate of enol ketonization and in the "uncatalyzed" reaction entirely by an increased rate of enolization.For hydroxide ion promoted enolate formation the phenyl effect appears roughly equally as an increase in the rate of enolate formation and a decrease in ketonization rate.It is suggested that the effects of a conjugated benzene ring on enol and enolate stability are fully expressed by the reactions of 2-indanone.
Discovery, biological evaluation, and crystal structure of a novel nanomolar selective butyrylcholinesterase inhibitor
Brus, Boris,Ko?ak, Urban,Turk, Samo,Pi?lar, Anja,Coquelle, Nicolas,Kos, Janko,Stojan, Jure,Colletier, Jacques-Philippe,Gobec, Stanislav
, p. 8167 - 8179 (2014)
Butyrylcholinesterase (BChE) is regarded as a promising drug target as its levels and activity significantly increase in the late stages of Alzheimer's disease. To discover novel BChE inhibitors, we used a hierarchical virtual screening protocol followed by biochemical evaluation of 40 highest scoring hit compounds. Three of the compounds identified showed significant inhibitory activities against BChE. The most potent, compound 1 (IC50 = 21.3 nM), was resynthesized and resolved into its pure enantiomers. A high degree of stereoselective activity was revealed, and a dissociation constant of 2.7 nM was determined for the most potent stereoisomer (+)-1. The crystal structure of human BChE in complex with compound (+)-1 was solved, revealing the binding mode and providing clues for potential optimization. Additionally, compound 1 inhibited amyloid β1-42 peptide self-induced aggregation into fibrils (by 61.7% at 10 μM) and protected cultured SH-SY5Y cells against amyloid-β-induced toxicity. These data suggest that compound 1 represents a promising candidate for hit-to-lead follow-up in the drug-discovery process against Alzheimer's disease.
Ironcarbonyl Complexes of 5,6-Dimethylidene-7-oxabicyclohept-2-ene Derivatives. Synthesis of Substituted Tricarbonyl(ortho-quinodimethane)iron Complexes and 2-Indanones
Bonfantini, Edia,Metral, Jean-Luc,Vogel, Pierre
, p. 1791 - 1797 (1987)
The 1-dimethoxymethyl-5,6-dimethylidene-7-oxabicyclohept-2-ene (9) has been prepared.On treatment with Fe2(CO)9, the endocyclic double bond C(2)=C(3) was coordinated first giving the corresponding exo-Fe(CO)4 complex 10.The latter reacted with Fe2(CO)9 and afforded cis heptacarbonyl-μ-hept-2-ene)>diiron (11) as a major product.On heating, 11 undervent deoxygenation of the 7-oxabicycloheptene moiety yielding tricarbonyliron (13).In MeOH, a concurrent, regioselective methoxycarbonylation was observed giving tricarbonyliron (14).Oxidative removal of the Fe(CO)3 moiety in 13 and 14 did not afford the expected ortho-quinodimethane derivatives but led to CO insertions giving 2,3-dihydro-2-oxo-1H-indene-4-carbaldehyde (2) and methyl 7-formyl-2,3-dihydro-2-oxo-1H-indene-5-carboxylate (21), respectively.
Bidentate Nitrogen-Ligated I(V) Reagents, Bi(N)-HVIs: Preparation, Stability, Structure, and Reactivity
Xiao, Xiao,Roth, Jessica M.,Greenwood, Nathaniel S.,Velopolcek, Maria K.,Aguirre, Jordan,Jalali, Mona,Ariafard, Alireza,Wengryniuk, Sarah E.
, p. 6566 - 6576 (2021/05/06)
Hypervalent iodine(V) reagents are a powerful class of organic oxidants. While the use of I(V) compounds Dess-Martin periodinane and IBX is widespread, this reagent class has long been plagued by issues of solubility and stability. Extensive effort has been made for derivatizing these scaffolds to modulate reactivity and physical properties but considerable room for innovation still exists. Herein, we describe the preparation, thermal stability, optimized geometries, and synthetic utility of an emerging class of I(V) reagents, Bi(N)-HVIs, possessing datively bound bidentate nitrogen ligands on the iodine center. Bi(N)-HVIs display favorable safety profiles, improved solubility, and comparable to superior oxidative reactivity relative to common I(V) reagents. The highly modular synthesis and in situ generation of Bi(N)-HVIs provides a novel and convenient screening platform for I(V) reagent and reaction development.
Sulfonium ion-promoted traceless Schmidt reaction of alkyl azides
Ardiansah, Bayu,Kakiuchi, Kiyomi,Morimoto, Tsumoru,Tanimoto, Hiroki,Tomohiro, Takenori
, p. 8738 - 8741 (2021/09/08)
Schmidt reaction by sulfonium ions is described. General primary, secondary, and tertiary alkyl azides were converted to the corresponding carbonyl or imine compounds without any trace of the activators. This bond scission reaction through 1,2-migration of C-H and C-C bonds was accessible to the one-pot substitution reaction.
Cycloaddition of carbon dioxide to epoxides by highly active constrained aluminum chloride complexes
Laiwattanapaisarn, Nattiya,Phomphrai, Khamphee,Virachotikul, Arnut
, p. 11039 - 11048 (2021/08/24)
The transformation of carbon dioxide (CO2) and epoxides to cyclic carbonates has gained much interest due to its low cost, abundance, low toxicity, and renewability. Therefore, novel constrained aluminum chloride complexes were developed based on bis(salicylimine) ligands for epoxides/CO2 coupling reactions. The five-membered rings attached to the aromatic rings were designed to enlarge the coordination pocket around the aluminum center as demonstrated by single-crystal X-ray crystallography. Addition of propylene oxide (PO) to a mixture of an aluminum chloride complex and tetrabutylammonium bromide (TBAB) rapidly gave (ligand)Al-OCH(Me)CH2Cl and (ligand)Al-OCH(Me)CH2Br in similar quantities. The anion exchange between (ligand)Al-Cl and TBAB was found to be faster than the ring-opening of PO. From a series of catalyst screening and optimization, the combination of catalyst 2g having no substituent on the aromatic rings and TBAB displayed very high activity (TOF up to 10?800 h-1) for the PO/CO2 coupling reaction. This catalyst system was extended to eleven more examples of epoxides. Moreover, excellent selectivity for cyclic carbonate production was observed for both terminal and internal epoxides.
g-C3N4/metal halide perovskite composites as photocatalysts for singlet oxygen generation processes for the preparation of various oxidized synthons
Corti, Marco,Chiara, Rossella,Romani, Lidia,Mannucci, Barbara,Malavasi, Lorenzo,Quadrelli, Paolo
, p. 2292 - 2298 (2021/04/12)
g-C3N4/metal halide perovskite composites were prepared and used for the first time as photocatalysts forin situ1O2generation to perform hetero Diels-Alder, ene and oxidation reactions with suitable dienes and alkenes. The standardized methodology was made applicable to a variety of olefinic substrates. The scope of the method is finely illustrated and the reactions afforded desymmetrized hydroxy-ketone derivatives, unsaturated ketones and epoxides. Some limitations were also observed, especially in the case of the alkene oxidations, and poor chemoselectivity was somewhere observed in this work which is the first application of MHP-based composites forin situ1O2generation. The experimental protocol can be used as a platform to further expand the knowledge and applicability of MHPs to organic reactions, since perovskites offer a rich variety of tuning strategies which may be explored to improve reaction yields and selectivities.
Asymmetric azidohydroxylation of styrene derivatives mediated by a biomimetic styrene monooxygenase enzymatic cascade
Franssen, Maurice C. R.,Hollmann, Frank,Martínez-Montero, Lía,Paul, Caroline E.,Süss, Philipp,Schallmey, Anett,Tischler, Dirk
, p. 5077 - 5085 (2021/08/16)
Enantioenriched azido alcohols are precursors for valuable chiral aziridines and 1,2-amino alcohols, however their chiral substituted analogues are difficult to access. We established a cascade for the asymmetric azidohydroxylation of styrene derivatives leading to chiral substituted 1,2-azido alcohols via enzymatic asymmetric epoxidation, followed by regioselective azidolysis, affording the azido alcohols with up to two contiguous stereogenic centers. A newly isolated two-component flavoprotein styrene monooxygenase StyA proved to be highly selective for epoxidation with a nicotinamide coenzyme biomimetic as a practical reductant. Coupled with azide as a nucleophile for regioselective ring opening, this chemo-enzymatic cascade produced highly enantioenriched aromatic α-azido alcohols with up to >99% conversion. A bi-enzymatic counterpart with halohydrin dehalogenase-catalyzed azidolysis afforded the alternative β-azido alcohol isomers with up to 94% diastereomeric excess. We anticipate our biocatalytic cascade to be a starting point for more practical production of these chiral compounds with two-component flavoprotein monooxygenases.
Negative allosteric modulators of the GluN2B NMDA receptor with phenylethylamine structure embedded in ring-expanded and ring-contracted scaffolds
Bechthold, Elena,Gawaskar, Sandeep,Robaa, Dina,Schepmann, Dirk,Schreiber, Julian A.,Seebohm, Guiscard,Sippl, Wolfgang,Temme, Louisa,Wünsch, Bernhard
supporting information, (2020/02/18)
A set of GluN2B NMDA receptor antagonists with conformationally restricted phenylethylamine substructure was prepared and pharmacologically evaluated. The phenylethylamine substructure was embedded in ring expanded 3-benzazocines 4 as well as ring-contracted tetralinamines 6 and indanamines 7. The ligands 4, 6 and 7 were synthesized by reductive alkylation of secondary amine 11, reductive amination of ketones 12 and 16 and nucleophilic substitution of nosylates 14 and 17. The moderate GluN2B affinity of 3-benzazocine 4d (Ki = 32 nM) translated into moderate cytoprotective activity (IC50 = 890 nM) and moderate ion channel inhibition (60% at 10 μM) in two-electrode voltage clamp experiments with GluN1a/GluN2B expressing oocytes. Although some of the tetralinamines 6 and indanamines 7 showed very high GluN2B affinity (e.g. Ki (7f) = 3.2 nM), they could not inhibit glutamate/glycine inducted cytotoxicity. The low cytoprotective activity of 3-benzazocines 4, tetralinamines 6 and indanamines 7 was attributed to the missing OH moiety at the benzene ring and/or in benzylic position. Docking studies showed that the novel GluN2B ligands adopt similar binding poses as Ro 25–6981 with the central H-bond interaction between the protonated amino moiety of the ligands and the carbamoyl moiety of Gln110. However, due to the lack of a second H-bond forming group, the ligands can adopt two binding poses within the ifenprodil binding pocket.
Homobenzylic Oxygenation Enabled by Dual Organic Photoredox and Cobalt Catalysis
McManus, Joshua B.,Griffin, Jeremy D.,White, Alexander R.,Nicewicz, David A.
supporting information, p. 10325 - 10330 (2020/07/27)
Activation of aliphatic C(sp3)-H bonds in the presence of more activated benzylic C(sp3)-H bonds is often a nontrivial, if not impossible task. Herein we show that leveraging the reactivity of benzylic C(sp3)-H bonds to achieve reactivity at the homobenzylic position can be accomplished using dual organic photoredox/cobalt catalysis. Through a two-part catalytic system, alkyl arenes undergo dehydrogenation followed by an anti-Markovnikov Wacker-type oxidation to grant benzyl ketone products. This formal homobenzylic oxidation is accomplished with high atom economy without the use of directing groups, achieving valuable reactivity that traditionally would require multiple chemical transformations.
