Substrate-controlled [4+1] and [3+2] annulations of ninhydrin-derived Morita-Baylis-Hillman carbonates to access polysubstituted furans and cyclopentenes.

The effective and mild [4+1] annulation of ninhydrin-derived MBH carbonates with α,ß-unsaturated ketones has been developed, providing a wide range of multisubstituted furans in high yields (up to 90%) with excellent ß-regioselectivities. In contrast, the polysubstituted cyclopentenes bearing dispiro-bisindanedione motifs were obtained via classical [3+2] annulations by employing ninhydrin-derived MBH carbonates with 2-arylidene-1,3-indandiones under the same catalytic conditions. Furthermore, the structures of two kinds of cycloadducts were straightforwardly confirmed through X-ray diffraction analysis.

Substrate-Controlled Diversity-Oriented Synthesis of Novel Polycyclic Frameworks via [4 + 2] and [3 + 2] Annulations of Ninhydrin-Derived MBH Adducts with 3,4-Dihydroisoquinolines.

Substrate-controlled diversity-oriented synthesis of polycyclic frameworks via [4 + 2] and [3 + 2] annulations between ninhydrin-derived Morita-Baylis-Hillman (MBH) adducts and 3,4-dihydroisoquinolines under similar reaction conditions have been developed. The reaction provides diversity-oriented synthesis of a series of novel and structurally complex spiro multi heterocyclic skeletons in good yields (up to 87% and 90%, respectively) with excellent diastereoselectivities (up to >25:1 dr). In particular, the switchable [4 + 2] and [3 + 2] annulation reactions are controlled by tuning the hydroxyl protecting group on the ninhydrin-derived MBH adduct to deliver structural diverse spiro[indene-2,2'-[1,3]oxazino[2,3-a]isoquinoline] and spiro[indene-2,1'-pyrrolo[2,1-a]isoquinoline], respectively. Furthermore, the relative configuration and chemical structure of two kinds of cycloadducts were confirmed through X-ray diffraction analysis.

Catalyst-Controlled Direct Oxysulfonylation of Alkenes by Using Sulfonylazides as the Sulfonyl Radical.

A copper/cobalt-catalyzed difunctionalization of alkenes with sulfonylazides and tert-butyl hydroperoxide has been achieved. This protocol provides an efficient and direct oxysulfonylation approach to ß-ketosulfones and ß-sulfonyl peroxides in moderate to good yields under mild conditions. This methodology applies sulfonylazides as a new sulfonyl radical source and features a wide substrate scope and good functional group tolerance.

Divergent Synthesis of Highly Substituted Tetrahydroquinolines and Cyclopentenes via Lewis Base Catalyzed Switchable [4 + 2] and [3 + 2] Annulations of MBH-Carbonates with Activated Olefins.

A highly selective and divergent synthesis which enabled access to various complex compounds is highly attractive in organic synthesis and medicinal chemistry. Herein, we developed an effective method for divergent synthesis of highly substituted tetrahydroquinolines via Lewis base catalyzed switchable annulations of Morita-Baylis-Hillman carbonates with activated olefins. The reaction displayed switchable [4 + 2] or [3 + 2] annulations via catalyst or substrate control, providing a diverse range of architectures which contained highly substituted tetrahydroquinolines or cyclopentenes with three contiguous stereocenters bearing a quaternary carbon center in high yields with excellent diastereoselectivities and regioselectivities. Furthermore, synthetic utility of this strategy was further highlighted by gram-scale experiments and simple transformations of the products.

Simultaneous Determination of Metabolites Related to Arginine Metabolism in Rat plasma by Hydrophilic Interaction Chromatography-Tandem Mass Spectrometry.

Arginine and its metabolites play important roles in pain and analgesia. This study aimed to develop a comprehensive quantification method for amino acids and metabolites related to arginine metabolism in rat plasma by hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS). Rat plasma was diluted to reduce the matrix effect and deproteinized with acetonitrile. The analytes were separated on a Syncronis HILIC column with a gradient elution. MS analysis was performed in positive ion mode with an electrospray ionization source using multiple reaction monitoring technology. All calibration curves for the 10 analytes showed good linear regression (R2 > 0.99). The limits of detection (LODs) were in the range of 0.9-13.4 µg/L. The established method was validated for intra-day and inter-day precisions (relative standard deviation [RSDs] < 6.21%) and accuracy (average recovery ranged from 87.34% to 100.35% with the RSD values less than 11.41%). This method was successfully applied to characterize dynamic alterations in the plasma of rats with neuropathic pain and thus provide service to explore the mechanism of action between metabolite changes and clinical disease.

Neurobiochemical biomarkers and other risk factors for post-traumatic acute stress disorder.

Trauma is a leading cause of mortality and morbidity around the world and many trauma patients could suffer from a series of cognitive and mental disorders including acute stress disorder (ASD). Yet, little research has been done to investigate the influencing factors and pathogenesis of post-traumatic ASD. Therefore, this study investigated main influencing factors and neurobiochemical biomarkers of ASD in trauma patients with a purpose of early clinical identification and intervention. The patients were followed up by general questionnaire and Acute Stress Disorder scale (ASDS). Using the diagnostic criteria of ASD, the study participants were divided into ASD group and non-ASD group. The generalized estimating equation (GEE) multivariate analysis suggested that life stress, sleep less than 8 h, trauma from road traffic crash, overall pain intensity, injury severity, overall fear after trauma were risk factors for ASD. Neutrophil to lymphocyte ratio (NLR) showed a downward trend in both groups (P < 0.05), and the ASD group was higher than the non-ASD group (P = 0.015). Glu to GABA ratio (GGR) in the ASD group were higher than the non-ASD group (P < 0.001). Both patient demographics and patient's condition could impact the risk of developing ASD after a major injury.

[3 + 2] cycloaddition of nonstabilized azomethine ylides and 2-benzothiazolamines to access imidazolidine derivatives.

A simple and practical method for the construction of 1,3,5-trisubstituted imidazolidine derivatives via [3 + 2] cycloaddition reaction has been developed. This reaction could smoothly proceed between nonstabilized azomethine ylides generated in situ and 2-benzothiazolamines to deliver a wide scope of differently substituted imidazolidines in high yields (up to 98%). The structure of one example was confirmed by X-ray single-crystal structure analysis.

Copper-Catalyzed Regio- and Stereoselective Sulfonylation of Alkynyl Imines with Sulfonyl Hydrazides: Access to (E)-ß-Sulfonyl Enones.

A copper-catalyzed sulfonylation of alkynyl imines with sulfonyl hydrazides has been developed, which exhibited excellent regio- and stereoselectivity and furnished a series of (E)-ß-sulfonyl enones in moderate to good yields. Mechanistic studies suggest that this strategy goes through a radical process.

Visible-Light Photocatalytic Reduction of Aryl Halides as a Source of Aryl Radicals.

Aryl- and heteroaryl units are present in a wide variety of natural products, pharmaceuticals, and functional materials. The method for reduction of aryl halides with ubiquitous distribution is highly sought after for late-stage construction of various aromatic compounds. The visible-light-driven reduction of aryl halides to aryl radicals by electron transfer provides an efficient, simple, and environmentally friendly method for the construction of aromatic compounds. This review summarizes the recent progress in the generation of aryl radicals by visible-light-driven reduction of aryl halides with metal complexes, organic compounds, semiconductors as catalysts, and alkali-assisted reaction system. The ability and mechanism of reduction of aromatic halides in various visible light induced systems are summarized, intending to illustrate a comprehensive introduction of this research topic to the readers.

Catalyst-Controlled Selectivity Switch in Three-Component Reaction: An NHC-Catalyzed Strategy for the Synthesis of δ-Lactone-Fused Spirobenzofuran-3-ones.

An efficient, three-component reaction of aldehydes and benzofuran-3-ones was developed. This process provides a new approach for the preparation of synthetically and biologically important spirobenzofuran-3-one derivatives with moderate-to-good yields under mild conditions. A switch of intramolecular to intermolecular domino Michael-aldol-lactonization leading to differential product formation was achieved by different NHCs catalysis.

TBAI-Catalyzed S-H and N-H Insertion Reactions of α-Diazoesters with Thiophenols and Amines under Metal-Free Conditions.

Mild, convenient, and effective TBAI-catalyzed S-H and N-H insertion reactions of α-diazoesters with thiophenols and aromatic amines under metal-free conditions have been described, furnishing a straightforward and general platform for the synthesis of various thioethers and 2-amino-2-oxoacetates in moderate to excellent yields. Moreover, this strategy features simple operation, mild conditions, broad substrate scope, and easy scale-up.

Synthesis of 1,3,5-trisubstituted pyrazoles via 1,3-dipolar cycloaddition of nitrile imines with ninhydrin-derived Morita-Baylis-Hillman carbonates.

An effective synthetic method for 1,3,5-trisubstituted pyrazoles via 1,3-dipolar cycloaddition reaction has been developed. This reaction could smoothly proceed between ninhydrin-derived Morita-Baylis-Hillman carbonates and nitrilimines to provide a wide scope of differently substituted pyrazoles in high yields (up to 95%). In addition, the reaction mechanism was also proposed to explain its regioselectivity.

Substrate-Controlled Regioselectivity Switchable [3 + 2] Annulations To Access Spirooxindole Skeletons.

The additive-free [3 + 2] annulation from isatins, amino acids with 2-styrylbenzoxazoles, was described, providing a series of functional and structurally complex 3,3'-pyrrolidinyl-spirooxindole derivatives containing four contiguous and two quaternary stereogenic centers in high yields (up to 95%) and excellent diastereoselectivities (up to >25:1 dr). Interestingly, the reaction exhibits switchable regioselectivity depending on the substrate of amino acids. With proline or thioproline as the substrate, the reaction afforded α-regioselective spirooxindole skeletons. In contrast, when piperidine acid is the substrate, the reaction provided γ-regioselective spirooxindole skeletons.

Facile Synthesis of Tricyclic 1,2,4-Oxadiazolines-Fused Tetrahydro-Isoquinolines from Oxime Chlorides with 3,4-Dihydroisoquinoline Imines.

A mild and efficient strategy for the synthesis of tricyclic 1,2,4-oxadiazolines-fused tetrahydro-isoquinolines derivatives via [3 + 2] cycloaddition reaction is reported. The reactions provided the functionalized tricyclic 1,2,4-oxadiazolines in high yields (up to 96%). This protocol is simple and easy to handle. Moreover, a gram-scale experiment further highlights the synthetic utility. The chemical structure of the product was determined by X-ray single-crystal structure analysis. A possible mechanism for this transformation is proposed to explain the reaction process.

Facile Synthesis of Sulfonyl Chlorides/Bromides from Sulfonyl Hydrazides.

A simple and rapid method for efficient synthesis of sulfonyl chlorides/bromides from sulfonyl hydrazide with NXS (X = Cl or Br) and late-stage conversion to several other functional groups was described. A variety of nucleophiles could be engaged in this transformation, thus permitting the synthesis of complex sulfonamides and sulfonates. In most cases, these reactions are highly selective, simple, and clean, affording products at excellent yields.

Evaluation of the phytochemicals and antioxidant activity of Lophatherum gracile Brongn based on chemical fingerprinting by HPLC with electrochemical detection.

A combinative method using high-performance liquid chromatography-electrochemical detection for fingerprinting and quantitative analysis was developed and successfully applied for the quality evaluation of Lophatherum gracile Brongn leaves collected from 21 geographical locations in China. In the fingerprint analysis, 18 common peaks were observed among the 21 samples, and 10 peaks were identified. Simultaneous quantification of the 10 components was conducted to interpret the variations in these compounds among the L. gracile Brongn leaves originating from different geographical locations. The correlation between the chromatograms and the antioxidant activities of the samples was further studied. The results indicated a linear correlation between the antioxidant activity and the total common peak areas of the fingerprints obtained by high-performance liquid chromatography-electrochemical detection. Importantly, it was found that high-performance liquid chromatography-electrochemical detection fingerprinting can not only determine the quantities of individual components present in such samples but also evaluate the antioxidant activities of the samples. The developed method is a valuable reference for the further study and development of L. gracile Brongn.

A copper iodide-catalyzed coupling reaction of benzofuran-3(2H)-ones with amines: an approach to α-ketoamides.

A CuI-catalyzed coupling reaction of benzofuran-3(2H)-ones with amines has been well established for the direct synthesis of α-ketoamides. This process involves C-O bond cleavage and C[double bond, length as m-dash]O/C-N bond formation. Mechanism studies indicated that this α-ketoamide formation reaction may involve a free radical process.

Synthesis of spiro[4.4]thiadiazole derivatives via double 1,3-dipolar cycloaddition of hydrazonyl chlorides with carbon disulfide.

An operationally simple and convenient synthesis method toward a series of diverse spiro[4.4]thiadiazole derivatives via double [3 + 2] 1,3-dipolar cycloaddition of nitrilimines generated in situ from hydrazonyl chlorides with carbon disulfide has been achieved under mild reaction conditions.

Facile synthesis of O-acylhydroxamates via reaction of oxime chlorides with carboxylic acids.

A simple and efficient method for the synthesis of O-acylhydroxamate derivatives from oxime chlorides and carboxylic acids was developed. The reaction affords clean and facile access to diverse O-acylhydroxamates in high yields (up to 85%). The chemical structure of a typical product was confirmed using single-crystal X-ray structure analysis.

Synthesis of N-alkoxyphthalimide derivatives via PIDA-promoted cross dehydrogenative coupling reaction.

A PIDA-promoted cross-dehydrogenative coupling reaction between N-hydroxyphthalimide (NHPI) and aryl ketones for efficient synthesis of N-alkoxyphthalimide products in moderate to good yields has been described. This methodology is distinguished by catalyst-free conditions, readily available starting materials, wide substrate scope and operational simplicity. In addition, a gram-scale reaction and synthetic transformation of the product into synthetically useful intermediates has been demonstrated.