Isochroman-3,4-dione and Tandem Aerobic Oxidation of 4-Bromoisochroman-3-one in the Highly Regio- and Diastereoselective Diels-Alder Reaction for the Construction of Bridged Polycyclic Lactones.

Herein we report two processes facilitated by diisopropylethylamine (DIPEA) for the synthesis of novel bridged polycyclic molecule analogues to natural products. The use of 4-bromoisochroman-3-one initiated an autoxidation reaction, followed by a Diels-Alder cycloaddition in the presence of electron-deficient dienophiles. Mechanistic studies revealed isochromane-3,4-dione as a key intermediate, which undergoes in situ dienolization/dearomatization followed by a [4 + 2] cycloaddition.

Lactone Enolates of Isochroman-3-ones and 2-Coumaranones: Quantification of Their Nucleophilicity in DMSO and Conjugate Additions to Chalcones.

Owing to stereoelectronic effects, lactones often deviate in reactivity from their open-chain ester analogues as demonstrated by the CH acidity (in DMSO) of 3-isochromanone (p = 18.8) and 2-coumaranone (p = 13.5), which is higher than that of ethyl phenylacetate (p = 22.

[Collapsing Glomerulopathy Secondary to Anabolic Steroids for Bodybuilding: A Case Series].

The abuse of anabolic androgenic steroids (AAS) for competitive (and non-competitive) purposes for bodybuilding practice is increasingly common. The consequences of these substances on the various organs are only partially known. Cases of FSGS following the use of AAS have been reported in the literature, even with evolution to ESKD.

The 3-(3-oxoisoindolin-1-yl)pentane-2,4-dione (ISOAC1) as a new molecule able to inhibit Amyloid β aggregation and neurotoxicity.

Amyloid β 1-42 (Aβ) protein aggregation is considered one of the main triggers of Alzheimer's disease (AD). In this study, we examined the in vitro anti-amyloidogenic activity of the isoindolinone derivative 3-(3-oxoisoindolin-1-yl)pentane-2,4-dione (ISOAC1) and its neuroprotective potential against the Aβ toxicity. By performing the Thioflavin T fluorescence assay, Western blotting analyses, and Circular Dichroism experiments, we found that ISOAC1 was able to reduce the Aβ aggregation and conformational transition towards β-sheet structures.

Correction: Monaco et al. Chiral Phase Transfer Catalysis in the Asymmetric Synthesis of a 3,3-Disubstituted Isoindolinone and Determination of Its Absolute Configuration by VCD Spectroscopy. 2020, , 2272.

In this note, we report a correction to the published article, , , 2272 [...

[Anti-MBG crescentic glomerulonephritis with negative immunofluorescence: case report and literature review].

Anti-glomerular basement membrane (anti-GBM) antibody disease is a rapidly progressive glomerulonephritis characterized by (i) positivity to anti-GBM in serum reacting with a specific antigen present in type IV collagen at both the glomerular and alveolar levels (ii) presence of crescent on light microscopy and positivity to linear deposits of IgG and C3 on immunofluorescence. In the classic variant, the clinic is that of a nephro-pneumological syndrome but there are variants. Rarely, the glomerular damage is pauci-immune.

Asymmetric Organocatalytic Mannich Reaction in the Synthesis of Hybrid Isoindolinone-Pyrazole and Isoindolinone-Aminal from Functionalized α-Amidosulfone.

The investigation of the reactivity of an α-amido sulfone derived from 2-formyl benzoate under organocatalytic conditions in the presence of acetylacetone allowed the synthesis of a new heterocyclic hybrid isoindolinone-pyrazole with high enantiomeric excess. Dibenzylamine was also used as a nucleophile to afford an isoindolinone with aminal substituent in 3-position in suitable selectivity. The use of Takemoto's bifunctional organocatalyst not only led to observed enantioselectivity but was also important in accomplishing the cyclization step in both cases.

A facile access to 1-substituted and unsubstituted 3-isoquinolinones Mannich or Sn2 initiated cascade reactions under catalyst-free conditions.

Herein we report new cascade processes for the easy access to 1-substituted and C-unsubstituted 3-isoquinolinones. The Mannich initiated cascade reaction led to the synthesis of novel 1-substituted 3-isoquinolinones under catalyst-free conditions in the presence of nitromethane and dimethylmalonate as nucleophiles without the use of any solvent. The optimization of the synthesis of the starting material in a more environmentally benign manner, allowed the identification of a common intermediate useful for the synthesis of C-unsubstituted 3-isoquinolinones as well.

Stereoselective Syntheses of Masked β-Amino Acid Containing Phthalides.

We herein report a protocol for the asymmetric aldol-initiated cascade addition of isoxazolidin-5-ones to -cyanobenzaldehydes by using 's bifunctional organocatalyst. This approach allows for the synthesis of various novel β-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.

Hyaluronic Acid in Biomedical Fields: New Trends from Chemistry to Biomaterial Applications.

The aim of this review is to give an updated perspective about the methods for chemical modifications of hyaluronic acid (HA) toward the development of new applications in medical devices and material engineering. After a brief introduction on chemical, structural and biological features of this important natural polysaccharide, the most important methods for chemical and physical modifications are disclosed, discussing both on the formation of new covalent bonds and the interaction with other natural polysaccharides. These strategies are of paramount importance in the production of new medical devices and materials with improved properties.

Scalable (Enantioselective) Syntheses of Novel 3-Methylated Analogs of Pazinaclone, ()-PD172938 and Related Biologically Relevant Isoindolinones.

Herein, we report the application of an efficient and practical KCO promoted cascade reaction of 2-acetylbenzonitrile in the synthesis of novel 3-methylated analogs of Pazinaclone and PD172938, belonging to isoindolinones heterocyclic class bearing a tetrasubstituted stereocenter. Organocatalytic asymmetric synthesis of the key intermediate and its transformation into highly enantioenriched 3-methylated analog of ()-PD172938 was also developed. These achievements can be of particular interest also for medicinal chemistry, since the methyl group is a very useful structural modification in the rational design of new and more effective bioactive compounds.

Asymmetric Cascade Aza-Henry/Lactamization Reaction in the Highly Enantioselective Organocatalytic Synthesis of 3-(Nitromethyl)isoindolin-1-ones from α-Amido Sulfones.

The asymmetric synthesis of novel 3-substituted isoindolinones is herein reported. A new cascade reaction was developed that consisted of the asymmetric nitro-Mannich reaction of suitable α-amido sulfones designed from 2-formyl benzoates, followed by the cyclization of the adducts. Very high enantioselectivities, up to 98% ee, and very good yields were obtained in the presence of the readily available neutral bifunctional organocatalyst derived from -1,2-diaminocyclohexane, which is known as Takemoto's catalyst.

Access to β-Alkylated γ-Functionalized Ketones via Conjugate Additions to Arylideneisoxazol-5-ones and Mo(CO)-Mediated Reductive Cascade Reactions.

1,4-Conjugate addition of ((chloromethyl)sulfonyl)benzenes to arylideneisoxazol-5-ones, followed by one-pot, N-selective trapping in the presence of electrophiles, was investigated. This strategy led to the synthesis of new, stable N-protected isoxazol-5-ones in good yields and high diastereolectivity. The study of the reactivity of obtained products in the presence of the Mo(CO)/HO system allowed the development of a cascade reaction leading to novel methyl ketones in high yields and unchanged dr bearing an uncommon chloromethinearylsulfonyl end group.

Synergistic Properties of Arabinogalactan (AG) and Hyaluronic Acid (HA) Sodium Salt Mixtures.

The properties of mixtures of two polysaccharides, arabinogalactan (AG) and hyaluronic acid (HA), were investigated in solution by the measurement of diffusion coefficients of water protons by DOSY (Diffusion Ordered SpectroscopY), by the determination of viscosity and by the investigation of the affinity of a small molecule molecular probe versus AG/HA mixtures in the presence of bovine submaxillary mucin (BSM) by HNMR spectroscopy. Enhanced mucoadhesive properties, decreased mobility of water and decreased viscosity were observed at the increase of AG/HA ratio and of total concentration of AG. This unusual combination of properties can lead to more effective and long-lasting hydration of certain tissues (inflamed skin, dry eye corneal surface, etc.

Base-Promoted Cascade Reactions for the Synthesis of 3,3-Dialkylated Isoindolin-1-ones and 3-Methyleneisoindolin-1-ones.

Cascade reactions of -carbonyl-substituted benzonitriles with ((chloromethyl)sulfonyl)benzenes as pronucleophiles led to new isoindolin-1-ones with a tetrasubstituted C-3 position or to ()-3-(sulfonyl-methylene)isoindolin-1-ones. The reactions start from readily available materials, are carried out under mild conditions, and do not require metal catalysis. Promoted only by the cheap and environmentally benign KCO as the base, up to six elemental steps can be combined in a single pot.

The First Highly Enantioselective Synthesis of 3-Sulfinyl-Substituted Isoindolinones Having Adjacent Carbon and Sulfur Stereocenters.

A highly stereoselective access to 3-sulfinyl-substituted isoindolinones has been achieved by a tandem organocatalytic addition/cyclization reaction of 2-carbobenzyloxy--tosylbenzylidenimine with thiols and succeeding diastereoselective oxidation with MCPBA. First, enantioenriched isoindolinone ,-acetals have been obtained through a dynamic kinetic asymmetric transformation induced by a bifunctional chiral thiourea organocatalyst. In turn, the newly created carbon stereocenter enabled a high diastereocontrol in the subsequent sulfoxidation.

Enantioselective Bifunctional Ammonium Salt-Catalyzed Syntheses of 3-CFS-, 3-RS-, and 3-F-Substituted Isoindolinones.

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 CFS- 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.

Lavender and coriander essential oils and their main component linalool exert a protective effect against amyloid-β neurotoxicity.

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 Aβ oligomers, a key molecular factor in the neurodegeneration of AD.

Chiral Phase Transfer Catalysis in the Asymmetric Synthesis of a 3,3-Disubstituted Isoindolinone and Determination of Its Absolute Configuration by VCD Spectroscopy.

In this work we report our endeavors toward the development of an asymmetric synthesis of a 3,3-disubstituted isoindolinone, dimethyl 2-(1-methyl-3-oxoisoindolin-1-yl)malonate, via asymmetric cascade reaction of 2-acetylbenzonitrile with dimethylmalonate and the determination of its absolute configuration (AC) by vibrational circular dichroism (VCD). Bifunctional ammonium salts, derived from 1,2-cyclohexanediamine in combination with inorganic bases under phase transfer conditions, were the most effective catalytic systems, leading to the target in high yields and moderate enantioselectivity. An efficient process of heterochiral crystallization allowed the increase of the enantiopurity up to 96% ee and in an acceptable overall yield.

An effective method for the determination of the enantio-purity of L-α-glycerophosphocholine (L-α-GPC).

Herein we describe for the first time a practical analytical method for determining the enantio-purity of L-α-glycerophosphocholine (L-α-GPC) by chiral derivatization. The use of a suitable chiral boronic acid allowed the formation of a mixture of two diastereomeric boronate esters whose ratio, carefully analyzed by HNMR spectroscopy, reflects L-α-GPC enantiomeric excesses. The determination of the enantiopurity of L-α-GPC furnishes convincing correlations with its manufacturing process.

Metal-Free Air Oxidation in a Convenient Cascade Approach for the Access to Isoquinoline-1,3,4()-triones.

Herein we describe a very useful application of the readily available trifunctional aromatic ketone methyl-2-(2-bromoacetyl)benzoate in reactions with primary amines. An unexpected in situ air oxidation that follows a cascade process allowed the access to a series of isoquinoline-1,3,4()-triones, a class of heterocyclic compounds of great interest containing an oxygen-rich heterocyclic scaffold. A modification of the original protocol, utilizing a Staudinger reaction in the presence of trimethylphosphine, was necessary for the synthesis of Caspase inhibitor trione with free NH group.

Asymmetric phase-transfer catalysed β-addition of isoxazolidin-5-ones to MBH carbonates.

A novel high yielding, and diastereoselective protocol for the synthesis of α-allylated highly functionalised β-amino acid derivatives by adding isoxazolidin-5-ones to MBH carbonates under asymmetric phase-transfer catalysis has been developed.