Asymmetric electrophilic functionalization of amino-substituted heteroaromatic compounds: a convenient tool for the enantioselective synthesis of nitrogen heterocycles.

The catalytic asymmetric electrophilic functionalization of the less reactive N-heteroaromatic compounds has been reported using the approach of the introduction of an exocyclic amino substituent. This strategy has allowed enantioselective Friedel-Crafts alkylation in pyrazoles, isoxazoles and isothiazoles, as well as in aminoindoles, aminobenzofurans and aminobenzothiophenes. Several stereoselective methods have been used for the 1,4-addition or 1,2-addition of these heteroaromatic compounds to different electrophiles employing organocatalysts or chiral metal complexes.

Net-clipping as a top-down approach for the prediction of topologies of MOFs built from reduced-symmetry linkers.

Reticular materials constructed from regular molecular building blocks (MBBs) have been widely explored in the past three decades. Recently, there has been increasing interest in the assembly of novel, intricate materials using less-symmetric ligands; however, current methods for predicting structure are not amenable to this increased complexity. To address this gap, we propose herein a generalised version of the net-clipping approach for anticipating the topology of metal-organic frameworks (MOFs) assembled from organic linkers and different polygonal and polyhedral MBBs.

Synthesis of α,α-Diaryl-α-amino Acid Precursors by Reaction of Isocyanoacetate Esters with -Quinone Diimides.

A novel procedure for the synthesis of α,α-diaryl-α-amino acid derivatives has been developed. Silver oxide catalyzes the conjugate addition of α-aryl isocyanoacetates to -quinone diimide, affording the corresponding α,α-diarylisocyano esters in excellent yields and regioselectivities in short reaction times. Acid hydrolysis of the isocyano group provides the corresponding amino acids bearing a diarylated tetrasubstituted carbon atom.

Organophotoredox 1,6-Addition of 3,4-Dihydroquinoxalin-2-ones to -Quinone Methides Using Visible Light.

An organophotoredox 1,6-radical addition of 3,4-dihidroquinoxalin-2-ones to -quinone methides catalyzed by Fukuzumi's photocatalyst is described under the irradiation of a HP Single LED (455 nm). The corresponding 1,1-diaryl compounds bearing a dihydroquinoxalin-2-one moiety (20 examples) are obtained with good to excellent yields under mild reaction conditions. Several experiments have been carried out in order to propose a reaction mechanism.

A Cu-BOX catalysed enantioselective Mukaiyama-aldol reaction with difluorinated silyl enol ethers and acylpyridine -oxides.

A Cu(II)/BOX complex catalyses the enantioselective addition of difluorinated silyl enol ethers to acylpyridine -oxides. The reaction provides difluorinated chiral tertiary alcohols of great interest in medicinal chemistry. These compounds are obtained in moderate to excellent yields and with high enantioselectivities.

Organocatalytic enantioselective Mannich reaction of isoxazol-5(4)-ones to isatin-derived ketimines.

An efficient organocatalytic asymmetric Mannich reaction between isoxazol-5(4)-ones and isatin-derived ketimines has been developed. A bifunctional squaramide/Brønsted base organocatalyst catalyzed the enantioselective Mannich addition to afford chiral 3-aminooxindoles bearing a tetrasubstituted stereocenter at C3 decorated with an isoxazole moiety in good yields and with excellent enantioselectivities. Additionally, several synthetic transformations were described showing the versatility of the prepared compounds.

Radical Addition of Dihydroquinoxalin-2-ones to Trifluoromethyl Ketones under Visible-Light Photoredox Catalysis.

A visible-light photocatalytic radical addition reaction of dihydroquinoxalin-2-ones to trifluoromethyl ketones has been established using Ru(bpy)Cl as photocatalyst, acetonitrile as solvent, and HP Single Blue LED as the source of light. The reaction provides a straightforward approach to the synthesis of dihydroquinoxalin-2-ones bearing a trifluoromethyl-substituted tertiary alcohol moiety in moderate to good yields under mild conditions.

Catalytic Diastereo- and Enantioselective Synthesis of Tertiary Trifluoromethyl Carbinols through a Vinylogous Aldol Reaction of Alkylidenepyrazolones with Trifluoromethyl Ketones.

A diastereo- and enantioselective organocatalytic aldol reaction between alkylidenepyrazolones and trifluoromethyl ketones leading to chiral tertiary alcohols bearing a trifluoromethyl group is presented. The methodology is based on the use of a bifunctional organocatalyst in order to activate the γ-hydrogen atoms of the alkylidenepyrazolone nucleophile and the carbonyl group of the trifluoromethylarylketone providing highly functionalized trifluoromethyl alcohols with moderate yields, excellent diastereoselectivity, and moderate to good enantioselectivity. Experiments monitoring the conversion by H NMR and the enantiomeric excess by HPLC with the reaction time showed that full conversion of the starting materials is not achieved and that the enantiomeric excess decreases upon extended times, probably due to the reversibility of the reaction.

Metal-Free Diastereo- and Enantioselective Dearomative Formal [3 + 2] Cycloaddition of 2-Nitrobenzofurans and Isocyanoacetate Esters.

The diastereo- and enantioselective dearomative formal [3 + 2] cycloaddition of 2-nitrobenzofurans and α-aryl-α-isocyanoacetate esters provides tricyclic compounds bearing the 3,8-dihydro-1-benzofuro[2,3-]pyrrole framework with three consecutive stereogenic centers. The reaction was enabled by a cupreine-ether organocatalyst. The reaction products were obtained with almost full diastereoselectivity and with excellent enantiomeric excesses for a number of substituted 2-nitrobenzofurans and isocyanoacetates.

Catalytic Diastereo- and Enantioselective Vinylogous Mannich Reaction of Alkylidenepyrazolones to Isatin-Derived Ketimines.

A valuable organocatalytic vinylogous Mannich reaction between alkylidenepyrazolones and isatin-derived ketimines has been successfully established. Squaramide organocatalyst, prepared from quinine, catalyzed the diastereo- and enantioselective vinylogous Mannich addition, affording a range of aminooxindole-pyrazolone adducts (24 examples) with excellent outcomes: up to 98% yield with complete diastereoselectivity and excellent enantioselectivity (up to 99% ee). Additionally, different synthetic transformations were performed with the chiral pyrazolone-oxindole adducts.

Collaborative manufacturing of ergonomic personal protective equipment (PPE) accessories to prevent infectious disease.

Throughout history there have been epidemics and pandemics of all kinds, however the most recent ones have been respiratory diseases that have had a significant effect on the society and that have caused high mortality rates. The preventive measures to minimize the risk of contagion by contact with infected surfaces include ergonomic accessories including personal protective equipment (PPE) to prevent hands to be in contact with surfaces that could be infected by viruses, bacteria, fungi, etc., thus avoiding infection by the usual entry routes (mouth, nose, and eyes) to the human body of highly contagious diseases such as COVID-19.

Preoperative Doppler Ultrasonography Allen Test for Radial Forearm Free Flap in Oral Cancer Reconstruction: Implications in Clinical Practice.

The Radial Forearm Free Flap (RFFF) is one of the most widely used microsurgical flaps for intraoral reconstruction. Although the Clinical Allen Test (CAT) is the most widely used preoperative diagnostic method with which to study the distal patency of the hand prior to the use of RFFF, several authors have reported potentially preventable serious vascular complications. This study included 87 consecutive patients with cancer of the oral cavity and RFFF as the flap of choice who were treated between 2010 and 2020, and compares the results of the Clinical Allen Test (CAT), the Doppler Allen Test (DAT) and the Surgical Allen Test (SAT).

Enantioselective Friedel-Crafts reaction of hydroxyarenes with nitroenynes to access chiral heterocycles via sequential catalysis.

Naphthols, hydroxyindoles and an activated phenol are reacted with differently substituted (E)-nitrobut-1-en-3-ynes using the commercially available Rawal's chiral squaramide. The corresponding β-nitroalkynes were obtained with good yields and excellent enantioselectivities. Moreover, dihydronaphthofurans can be accessed via silver catalysed cyclization in a tandem one-pot procedure, with high preservation of the optical purity.

Visible-light-accelerated amination of quinoxalin-2-ones and benzo[1,4]oxazin-2-ones with dialkyl azodicarboxylates under metal and photocatalyst-free conditions.

A direct sp3 C-H amination of cyclic amines (dihydroquinoxalinones and dihydrobenzoxazinones) with dialkyl azo dicarboxylates accelerated by visible-light irradiation under metal and photocatalyst-free conditions is described. This protocol features very mild reaction conditions for the synthesis of aminal quinoxaline and benzoxazine derivatives with good to high yields (up to 99%). These aminal derivatives respresent versatile building blocks for the divergent synthesis of quinoxalin-2-one derivatives.

Prebiotic effects of pectooligosaccharides obtained from lemon peel on the microbiota from elderly donors using an continuous colon model (TIM-2).

The development of new prebiotics capable of modulating the gut microbiota in the elderly has become an area of great interest due to the particular vulnerability and frailty of this population. In the present work, mixtures of pectin-derived oligosaccharides (POS) were manufactured from lemon peel waste and evaluated for their capability to modulate the gut microbiota using, as inoculum, a pool of faeces from elderly donors. Both changes in the microbiota and the metabolic activity were assessed and compared with commercial fructooligosaccharides (FOS) and the standard ileal efflux medium (SIEM) using the TIM-2 in vitro colon model.

Photocatalytic Giese Addition of 1,4-Dihydroquinoxalin-2-ones to Electron-Poor Alkenes Using Visible Light.

The visible-light photoredox-catalyzed coupling of 1,4-dihydroquinoxalin-2-ones and Michael acceptors was achieved using Ru(bpy)Cl as the photocatalyst and (PhO)POH as an additive. The optimized reaction conditions provide a good yield for the radical conjugate addition products (44 examples) with a wide range of structurally different Michael acceptors. A gram scale reaction using sunlight irradiation is also described.

Enantioselective zinc-mediated conjugate alkynylation of saccharin-derived 1-aza-butadienes.

The enantioselective 1,4-alkynylation of conjugated imines derived from saccharin with aryl- and alkyl-substituted terminal alkynes has been achieved. The reaction mediated by diethylzinc in the presence of a catalytic amount of a bis(hydroxy)malonamide chiral ligand provides the corresponding imines bearing a propargylic stereocenter with moderate yields and fair to excellent enantioselectivities.

Potential of High- and Low-Acetylated Galactoglucomannooligosaccharides as Modulators of the Microbiota Composition and Their Activity: A Comparison Using the Model of the Human Colon TIM-2.

High- and low-acetylated galactoglucomannooligosaccharides (GGMOS_Ac and GGMOS, respectively) were assayed as substrates in the TIM-2 colon model using, as inoculum, fecal microbiota from the elderly. The effects on the microbiota and their activity were also compared to a standard ileal efflux medium (SIEM). GGMOS resulted in higher organic acid productions and higher short-chain fatty acids/total organic acid molar ratios.

Manufacture of Platform Chemicals from Pine Wood Polysaccharides in Media Containing Acidic Ionic Liquids.

wood samples were subjected to chemical processing for manufacturing furans and organic acids from the polysaccharide fractions (cellulose and hemicellulose). The operation was performed in a single reaction stage at 180 or 190 °C, using a microwave reactor. The reaction media contained wood, water, methyl isobutyl ketone, and an acidic ionic liquid, which acted as a catalyst.

An Approach to Sustainable Metrics Definition and Evaluation for Green Manufacturing in Material Removal Processes.

Material removal technologies should be thoroughly analyzed not only to optimize operations but also to minimize the different waste emissions and obtain cleaner production centers. The study of environmental sustainability in manufacturing processes, which is rapidly gaining importance, requires activity modeling with material and resource inputs and outputs and, most importantly, the definition of a balanced scorecard with suitable indicators for different levels, including the operational level. This paper proposes a metrics deployment approach for the different stages of the product life cycle, including a conceptual framework of high-level indicators and the definition of machining process indicators from different perspectives.

Organocatalytic enantioselective aminoalkylation of pyrazol-3-ones with aldimines generated in situ from α-amido sulfones.

Herein, an efficient asymmetric aminoalkylation of pyrazolones with α-amido sulfones catalyzed by a quinine-derived squaramide in dichloromethane/aqueous media has been established. A variety of chiral amines were obtained with high yields (up to 98%) and excellent enantioselectivities (up to 99% ee). The corresponding products are transformed into optically active acetylated pyrazoles after treatment with Ac2O/Et3N, because of the instability of some adducts.

A poly(glycidyl-co-ethylene dimethacrylate) nanohybrid modified with β-cyclodextrin as a sorbent for solid-phase extraction of phenolic compounds.

A hybrid material made of β-cyclodextrin anchored to a polymeric network is described and evaluated as a sorbent for solid-phase extraction of phenolic compounds (phenol, cresol isomers, 2-methoxy-4-vinylphenol, 4-ethylphenol, 4-vinylphenol, 4-ethylguaiacol, guaiacol, and eugenol). The polymeric backbone of the sorbent consists of a poly(glycidyl-co-ethylene dimethacrylate) network, whose surface has been modified with β-cyclodextrin by a click-chemistry based procedure. The resulting material has been characterized by different techniques, and it has shown to be viable as a sorbent for its use in extraction cartridges.

A Combination of Visible-Light Organophotoredox Catalysis and Asymmetric Organocatalysis for the Enantioselective Mannich Reaction of Dihydroquinoxalinones with Ketones.

An enantioselective photooxidative Mannich reaction of dihydroquinoxalinones with ketones by the merger of organophotoredox and asymmetric organocatalysis is described. This protocol features very mild reaction conditions using simple and cheap catalysts (Eosin Y and ()-Proline) for the synthesis of chiral quinoxaline derivatives with good to high yields (up to 94%) and excellent enantioselectivities (up to 99% ee).

Catalytic Diastereo- and Enantioselective Synthesis of 2-Imidazolinones.

Chiral cyclic ureas (2-imidazolinones) were prepared by the reaction of nitrones and isocyanoacetate esters using a multicatalytic system that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag as a Lewis acid. The reaction could be achieved with a range of nitrones derived from aryl- and cycloalkylaldehydes with moderate diastereo- and good enantioselectivity. A plausible mechanism involving an initial formal [3 + 3] cycloaddition of the nitrone and isocyanoacetate ester, followed by rearrangement to an aminoisocyanate and cyclization to the imidazolinone, is proposed.

Almotriptan: a review of 20 years' clinical experience.

: Almotriptan (ALT), a serotonin 5-HT agonist has been used in the acute treatment of migraine with or without aura for 20 years, accumulating data on more than 15,000 patients in studies and from an estimated >150 million treated migraine attacks in daily clinical practice. The last major review of ALT was written almost 10 years ago. The current narrative review provides an overview of the experience gained with almotriptan over that time, and highlights data published in the last decade.