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2‐Cyanobenzaldehye (also called 2‐formylbenzonitrile) and related 2‐acylbenzonitriles belong to a class of bifunctional aromatic compounds that emerged as useful starting materials in developing efficient cascade‐type reactions leading to different heterocyclic compounds. The variety of sometimes unpredictable mechanisms that rise from these structurally simple starting materials renders this class of compounds unique to afford, through divergent cascade reactions, heterocycles like isoindolinones, phthalides (also known with the name of isobenzofuranones), imidates, and in less extent isoindolin‐1‐imine, six‐ and seven‐membered heterocycles, porphyrins, also in asymmetric way exploiting different organocatalytic activation modes. To give a picture, this chemistry can be associated to Goldberg variations which stem from a common motive in a pressing and surprising way. In this Review, emphasis is also given to the synthetic methods for the access to substituted 2‐cyanobenzaldehydes and 2‐acylbenzonitriles which allowed to enlarge the scope of the described cascade reactions. [ABSTRACT FROM AUTHOR]

We herein report a protocol for the asymmetric aldol‐initiated cascade addition of isoxazolidin‐5‐ones to ortho‐cyanobenzaldehydes by using Takemoto's bifunctional organocatalyst. This approach allows for the synthesis of various novel β2,2‐amino acid‐phthalide conjugates with good enantio‐ and diastereoselectivities in reasonable yields and the further ring‐opening of these compounds to acyclic carboxylic acid derivatives was demonstrated too. [ABSTRACT FROM AUTHOR]

We herein report the ammonium salt‐catalyzed synthesis of chiral 3,3‐disubstituted isoindolinones bearing a heteroatom functionality in the 3‐position. A broad variety of differently substituted CF3S‐ and RS‐derivatives were obtained with often high enantioselectivities when using Maruoka's bifunctional chiral ammonium salt catalyst. In addition, a first proof‐of‐concept for the racemic synthesis of the analogous F‐containing products was obtained as well, giving access to one of the rare examples of a fairly stable α‐F‐α‐amino acid derivative. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder leading to cognitive deficits and cognitive decline. Since no cure or preventing therapy is currently available to counteract AD, natural‐derived compounds are investigated to find new potential neuroprotective agents for its treatment. In the present study, we tested the neuroprotective effect of lavender and coriander essential oils (EOs) and their main active constituent linalool, against the neurotoxicity elicited by Aβ1‐42 oligomers, a key molecular factor in the neurodegeneration of AD. Importantly, our findings on neuronally differentiated PC12 cells exposed to Aβ1‐42 oligomers are in accordance with previous in vivo studies reporting the neuroprotective potential of lavender and coriander EOs and linalool. We found that lavender and coriander EOs at the concentration of 10 μg/mL as well as linalool at the same concentration were able to improve viability and to reduce nuclear morphological abnormalities in cells treated with Aβ1‐42 oligomers for 24 hours. Lavender and coriander EOs and linalool also showed to counteract the increase of intracellular reactive oxygen species production and the activation of the pro‐apoptotic enzyme caspase‐3 induced by Aβ1‐42 oligomers. Our findings provide further evidence that these EOs and their main constituent linalool could be natural agents of therapeutic interest against Aβ1‐42‐induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Herein we report the first asymmetric Michael reaction of arylidene‐isoxazol‐5‐one with 1,3‐diesters. Despite complex tautomer equilibria of the obtained Michael adducts, the one‐pot entrapping strategy by the aid of different electrophiles/protecting groups led to the selective isolation of diverse N‐substituted isoxazol‐5‐ones in very high overall yield and good enantioselectivity. Asymmetric three components Michael/electrophilic tautomer‐entrapping and four‐component Knoevenagel/Michael/electrophilic‐tautomer‐entrapping methodologies have also been developed. The enantiopurity of several final products was further increased after crystallization, up to > 99.9:0.1 er in good overall yields. [ABSTRACT FROM AUTHOR]

Integrated experimental and computational approach provides a rationale for the mode of action of cinchona‐based alkaloids as chiral receptors in the observed dynamic chiral resolution of the titled tandem reaction. In particular, a mechanism based on a dynamic kinetic asymmetric transformation has been unravelled in detail. Furthermore, the crucial role of "distal" H‐bonding donor functionality in directing the enantioselectivity reversal of homochiral cinchona‐based catalysts has been convincingly explained. The access to enantiopure tertiary isoindolinone N,S‐acetals has been achieved for the first time. [ABSTRACT FROM AUTHOR]

Herein we report new methodologies for the synthesis of the challenging ketones 2‐cyanobenzophenones, based on Suzuki‐Miyaura type cross‐coupling reactions and very mild oxidation of 2‐benzylbenzonitriles. The investigation of the reactivity of the obtained ketones highlighted a very good electrophilicity in the presence of mild carbon‐ and hetero‐nucleophiles, allowing the synthesis of 3,3‐disubstituted isoindolin‐1‐ones. All the developed methodologies are highly efficient and tolerate combinations of functional groups present on both the aromatic rings. [ABSTRACT FROM AUTHOR]

2‐Acetylbenzonitriles have been conveniently synthesized by the oxidation of the respective 2‐ethylbenzonitriles, combining in a one‐pot procedure radical bromination and hydrolysis reactions. The obtained ketones reacted under very mild conditions with carbon and hetero nucleophiles to give a wide range of 3,3‐disubstituted isoindolinones in yields of 80–99 % by a tandem process consisting of an addition step and a subsequent Dimroth‐type rearrangement. Among the tested nucleophiles, the addition of water in the presence of a catalytic amount of KOH allowed a convenient access to an unprecedented variety of novel 3‐hydroxy‐3‐methylisoindolinones. [ABSTRACT FROM AUTHOR]

The effectiveness of a series of chiral phase transfer catalysts in of active methylene compounds with 2-cyanobenzaldehyde leading to chiral 3-substituted isoindolinones and fused benzoindolizidinones has been investigated. High yields and moderate enantiomeric excesses (e.e.s) were achieved employing a chiral phase-transfer catalyst derived from bifunctional urea-quinine. Moreover, an efficient process of heterochiral crystallization, performed on moderately enantioenriched compounds, led to an impressive increase of the enantiopurity up to 93% e.e.s. [ABSTRACT FROM AUTHOR]

An efficient potassium carbonate-catalyzed synthesis of 3-substituted isoindolinones through tandem aldol/cyclization reactions of active methylene compounds with 2-cyanobenzaldehyde is described. The utility of the obtained isoindolinones has been demonstrated through an exploration of the chemical space by employing a series of interesting methodologies that led to diverse, highly functionalized compounds. Among them, a surprisingly straightforward potassiumcarbonate-catalyzed double tandem reaction led to tricyclic hemiaminal derivatives. [ABSTRACT FROM AUTHOR]

A tandem aldol-heterocyclization-rearrangement reaction and one-pot sequential Michael addition allowed a direct access to highly functionalized 3-isoindolinones containing quaternary carbon centers. The desired products are obtained under mild conditions and in short reaction times by galvanostatic electrolysis in a divided cell. A further tandem intramolecular heterocyclization reaction leading to synthetically relevant hemiaminal derivatives has been established with suitable Michael acceptors. [ABSTRACT FROM AUTHOR]

With the aim of identifying novel lead compounds active against emergent human infectious diseases, a series of 2,3-dihydro-4H-pyridinone derivatives has been prepared and evaluated for antiviral activity. Compounds were evaluated in vitro in cell-based assays for cytotoxicity and against a wide spectrum of viruses. In the antiviral screening, several compounds showed to be fairly active against viruses belonging to the Flaviviridae family. The Pestiviruses (bovine viral diarrhoea virus) were inhibited by cis (CC > 100 μ; EC = 14 μ), compounds cis and showed a significant activity against Flaviviruses (Yellow Fever Virus) (CC > 100 μ; EC = 18 μ, CC > 100 μ; EC = 10 μ). Among these, compound displayed great inhibitory activity against Hepaciviruses (hepatitis C virus) in replicon assay [CC > 100 μ; EC(1b) = 4 μ]. In vitro inhibitory activity against the HCV RNA-dependent RNA polymerase (NS5B) of title compounds is discussed. The antiviral screening of viral strains indicated that compound can be selected as promising tool in novel anti-flaviviruses development. A series of 2,3-dihydro-4H-pyridinone derivatives has been prepared and evaluated for antiviral activity. In the antiviral screening, several compounds showed to be fairly active against viruses belonging to the Flaviviridae family. Among these, three compouds (, and ) showed an interesting activity against YFV, BVDV and HCV with an EC in a low micromolar range [ABSTRACT FROM AUTHOR]

Investigates the mechanism of immediate and delayed hypersensitivity to mite antigens in atopic dermatitis (AD). Incidence of AD among children; Role of delayed hypersensitivity in the development of AD; Clinical manifestations of the disease.

A chiral phase transfer catalyst is used in the reaction of 2-cyanobenzaldehyde with active methylene compounds. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor on the treatment of generalized morphea and lichen sclerosus by sulphasalazine, published in the May 1, 1999 issue of the journal "Journal of European Academy of Dermatology and Venereology."

The synthesis of 3-substituted isoindolinones employing a K2CO3-catalyzed tandem aldol/cyclization/rearrangement reaction of 2-cyanobenzaldehyde with malonates is reported. [ABSTRACT FROM AUTHOR]