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A highly efficient, atom-economical α-allylation reaction of NH 2 -unprotected amino acid esters and alkynes is achieved by chiral aldehyde/palladium combined catalysis. A diverse range of α,α-disubstituted nonproteinogenic α-amino acid esters are produced in 31-92% yields and 84-97% ee values. The allylation products are utilized for the synthesis of drug molecule BMS561392 and other chiral molecules possessing complex structures. Mechanistic investigations reveal that this reaction proceeds via a chiral aldehyde-/palladium-mediated triple cascade catalytic cycle.

Background: Mutations in mitochondrial tRNA ( mt-tRNA ) genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus (T2DM). We pre-viously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA Trp A5514G and tRNA Ser(AGY) C12237T variants, however, the effects of these mt-tRNA variants on T2DM progression are largely unknown., Aim: To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic, molecular, and biochemical levels., Methods: Cytoplasmic hybrid (cybrid) cells carrying both m.A5514G and m.C12237T variants, and healthy control cells without these mitochondrial DNA (mtDNA) variants were generated using trans-mitochondrial technology. Mitochondrial features, including mt-tRNA steady-state level, levels of adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mtDNA copy number, nicotinamide adenine dinucleotide (NAD + )/NADH ratio, enzymatic activities of respiratory chain complexes (RCCs), 8-hydroxy-deo-xyguanine (8-OhdG), malondialdehyde (MDA), and superoxide dismutase (SOD) were examined in cell lines with and without these mt-tRNA variants., Results: Compared with control cells, the m.A5514G variant caused an approximately 35% reduction in the steady-state level of mt-tRNA Trp ( P < 0.0001); however, the m.C12237T variant did not affect the mt-tRNA Ser(AGY) steady-state level ( P = 0.5849). Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells: ATP, MMP, NAD + /NADH ratio, enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells ( P < 0.05 for all measures). By contrast, the levels of ROS, 8-OhdG and MDA were significantly increased ( P < 0.05 for all measures), but mtDNA copy number was not affected by m.A5514G and m.C12237T variants ( P = 0.5942)., Conclusion: The m.A5514G variant impaired mt-tRNA Trp metabolism, which subsequently caused mitochondrial dysfunction. The m.C12237T variant did not alter the steady-state level of mt-tRNA Ser(AGY) , indicating that it may be a modifier of the m.A5514G variant. The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Even though catalytic asymmetric bifunctionalization of allenes has been extensively studied, almost all of the reported examples have been achieved in a two-component manner. In this study, we report a highly efficient asymmetric bifunctionalization of allenes with iodohydrocarbons and NH 2 -unprotected amino acid esters. The adopted chiral aldehyde/palladium combined catalytic system precisely governs the chemoselectivity, regioselectivity, and stereoselectivity of this three-component reaction. A wide range of substituted aryl iodides, allenes and amino acid esters can well participate in this reaction and deliver structurally diverse α,α-disubstituted α-amino acid esters with excellent experimental outcomes. One of the resulting products is utilized for the total synthesis of the molecule ( S , R )-VPC01091., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Axially chiral thioethers and sulfoxides emerge as two pivotal classes of ligands and organocatalysts, which have remarkable features in the stereoinduction of various asymmetric transformations. However, the lack of easy methods to access such molecules with diverse structures has hampered their broader utilization. Herein, an oxidative kinetic resolution for sulfides using a chiral bifunctional squaramide as the catalyst with cumene hydroperoxide as the terminal oxidant is established. This asymmetric approach provides a variety of axially chiral thioethers as well as sulfoxides bearing both axial and central chirality, with excellent diastereo- and enantioselectivities. This catalytic system also successfully extends to the kinetic resolution of benzothiophene-based sulfides. Preliminary mechanism investigation indicates that the multiple hydrogen bonding interactions between the bifunctional squaramide catalyst and substrates play a crucial role in determining the enantioselectivity and reactivity., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Despite the long-standing exploration of the catalytic asymmetric Tsuji-Trost allylation reaction since the mid-20th century, most reported instances have adhered to a two-component approach. Here, we present a remarkably efficient three-component asymmetric allylation reaction enabled by the collaborative action of chiral aldehyde and palladium. A diverse array of NH 2 -unprotected amino acid esters, aryl or alkenyl iodides, and allyl alcohol esters exhibit robust participation in this reaction, resulting in the synthesis of structurally diverse non-proteinogenic α-amino acid esters with favorable experimental outcomes. Mechanistic investigations reveal the dominance of the allylation/Heck coupling cascade in reactions involving electron-rich aryl iodides, while the Heck coupling/allylation cascade emerges as the dominant pathway in reactions involving electron-deficient aryl iodides. This chiral aldehyde/palladium combining catalytic system precisely governs the chemoselectivity of C -allylation and N -allylation, the regioselectivity of linear and branched allylation, and the enantioselectivity of C -allylation products., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

ConspectusThe development of catalytic activation modes provides a reliable and effective platform for designing new enantioselective reactions and preparing chiral molecules with diverse structures. Chiral aldehyde catalysis is an attractive concept in asymmetric catalysis, which utilizes a chiral aldehyde catalyst to promote the asymmetric hydroamination of allylic amines, the asymmetric α-functionalization of primary amines, or the asymmetric transamination of α-keto esters. Typically, the chiral aldehyde-catalyzed asymmetric α-functionalization of primary amines provides an efficient and straightforward method for the synthesis of α-functionalized chiral amines, which does not require any additional protection or deprotection manipulations of the amine group. However, achieving catalytic stereoselective transformations with high efficiency and enantioselectivity by this strategy has remained an intractable challenge.This Account summarizes our endeavors in the development and application of chiral aldehyde catalysis. Using a chiral aldehyde as a catalyst, we reported the catalytic asymmetric α-C alkylation of 2-aminomalonate with 3-indolylmethanol in 2014, which represents the first chiral aldehyde-catalyzed asymmetric α-functionalization of an activated primary amine. Subsequently, several axially chiral aldehyde catalysts were continuously prepared by using chiral BINOL as the starting material, and their applications in asymmetric synthesis were explored. On the one hand, they were used as organocatalysts to realize the various transformations of α-amino acid esters, such as asymmetric 1,4-addition toward conjugated enones/α,β-unsaturated diesters and cyclic 1-azadienes as well as asymmetric α-arylation/allylation and benzylation with corresponding halohydrocarbons. Notably, taking advantage of the difference in the distribution of catalytic sites between two chiral aldehyde catalysts, we disclosed chiral aldehyde-catalyzed diastereodivergent 1,6-conjugated addition and Mannich reactions. On the other hand, the potential for the cooperative catalysis of a chiral aldehyde with a transition metal has also been demonstrated. Enabled by the combination of a chiral aldehyde, a palladium complex, and a Lewis acid, the enantioselective α-allylation of amino acid esters with allyl alcohol esters was established. Moreover, the ternary catalytic system has been successfully used for the α-functionalization of amino acid esters with 1,3-dienes, allenes, allenylic alcohol esters, 1,3-disubstituted allyl alcohol esters, and arylmethanol esters as well as the asymmetric cascade Heck-alkylation reaction. The combination of a chiral aldehyde and nickel complex allows for the asymmetric α-propargylation of amino acid esters with propargylic alcohol esters and provides excellent enantioselectivities. These transformations provide a large library of optically active amines and amino acids. With those chiral amino acid esters as key building blocks, the synthesis or formal synthesis of multiple natural products and biologically significant unnatural molecules was accomplished. This includes the stereodivergent synthesis of natural pyrrolizidine alkaloid NP25302 and the formal synthesis of natural product ( S )-hypoestestatin 1 and manzacidin C, clinical candidate compound (+)-AG-041R, and somatostatin mimetics. It is fully anticipated that chiral aldehyde catalysis will soon witness rapid expansion both in the development of novel asymmetric transformations and in innovative applications for constructing optically active nitrogen-containing molecules with significant values.

Hedysarumqilianshanense sp. nov. (Fabaceae, Hedysareae) is described and illustrated from the Qilianshan Mountains in Gansu, China. This new species is similar to H.przewalskii , but can be distinguished by its corolla being light purple to purple, standard 15-19 mm long, wings 14-16 mm long, keels 16-19 mm long, and the ovary and legume being glabrous. The new species can be easily distinguished from H.neglectum Ledeb. by its bract being shorter than the pedicel, and the ovary and legume being glabrous. Phylogenetic tree based on the nuclear ITS and ETS sequences shows that H.qilianshanense is sister to H.przewalskii , while the tree based on the plastid psbA-trnH , trnC-petN , trnL-F , trnS-G and petN-psbM sequences shows H.qilianshanense as sister to a clade consisting of H.hedysaroides , H.inundatum , H.americanum and H.neglectum . The new species is a diploid with the chromosome number 2n = 14. Based on morphological, phylogenetic and karyotypic evidence, the new species may originate from an ancient homoploid hybrid speciation event., Competing Interests: The authors have declared that no competing interests exist., (Pei-Liang Liu, Qian-Xi Guo, Jian-Qi Zhang, Lu-Lu Xun, Yuan Lu, Ming Yue.)

Aiming at the reported chiral synthons leading to manzacidins A and D, here we report a highly efficient catalytic asymmetric α-allenylic alkylation reaction of NH 2 -unprotected amino acid esters that is promoted by combined chiral aldehyde/palladium catalysis. Fifty examples of unnatural α,α-disubstituted amino acid esters are reported with good-to-excellent yields and stereoselectivities. Based on this methodology, a key intermediate leading to manzacidin C and its other three stereoisomers is prepared accordingly.

A chiral aldehyde/palladium catalysis-enabled asymmetric α-allylation of NH 2 -unprotected amino acid esters with 1,3-disubstituted allyl acetates is described in this work. With the utilization of different chiral phosphine ligands, both the anti- and syn- selective allylation reactions are achieved enantioselectively. A series of α,α-disubstituted amino acid esters bearing two adjacent chiral centers are produced in moderate-to-excellent yields, diastereoselectivities, and enantioselectivities.

The first catalytic asymmetric cascade Heck-alkylation reaction of NH 2 -unprotected amino acid esters with N -(2-iodophenyl)allenamides is reported in this work. Under the promotion of a combining catalytic system comprising a chiral aldehyde, a chiral palladium complex, and the Lewis acid ZnCl 2 , the title reaction takes place smoothly, giving optically active α-alkyl tryptophan derivatives in moderate to good yields and excellent enantioselectivities. The target products can be converted into other structurally complex chiral indoles without the loss of enantioselectivities.

The direct catalytic α-hydrocarbylation of readily available amino acids with halohydrocarbons is one of the most straightforward methods leading to α,α-disubstituted non-proteinogenic α-amino acid compounds. However, all the reported methodologies depend on N-protected amino acids as starting materials. Herein, we report on three highly efficient aldehyde-catalyzed direct α-hydrocarbylations of N-unprotected amino acid esters with aryl-, allyl-, and benzyl halides. By promoting a simple chiral BINOL-aldehyde catalyst or combining catalysts of a chiral aldehyde and Lewis acid ZnCl 2 , the asymmetric α-arylation, α-allylation, and α-benzylation of amino acid esters with the corresponding halohydrocarbons proceed smoothly, producing α,α-disubstituted α-amino acids in moderate-to-high yields and good-to-excellent enantioselectivities. The asymmetric α-arylation reaction can be applied in the formal synthesis of the clinical candidate compound (+)-AG-041R. Based on the results given by control experiments, three reaction models are proposed to illustrate the stereoselective-control outcomes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The variation and correlation of leaf economics and vein traits are crucial for predicting plant ecological strategies under different environmental changes. However, correlations between these two suites of traits and abiotic factors such as soil water and nitrogen content remain ambiguous. We measured leaf economics and vein traits as well as soil water and nitrogen content for two different shade-tolerant species ( Betula platyphylla and Acer mono ) in four mixed broadleaved-Korean pine ( Pinus koraiensis ) forests along a latitudinal gradient in Northeast China. We found that leaf economics traits and vein traits were decoupled in shade-intolerant species, Betula platphylla , but significantly coupled in a shade-tolerant species, A. mono. We found stronger correlations among leaf traits in the shade tolerant species than in the shade intolerant species. Furthermore, leaf economic traits were positively correlated with the soil water gradient for both species, whereas vein traits were positively correlated with soil water gradient for the shade intolerant species but negatively correlated in the shade tolerant species. Although economic traits were positively correlated with soil nitrogen gradient in shade intolerant species but not correlated in shade tolerant species, vein traits were negatively correlated with soil nitrogen gradient in shade tolerant species but not correlated in shade intolerant species. Our study provides evidence for distinct correlations between leaf economics and vein traits and local abiotic factors of species differing in light demands. We recommend that the ecological significance of shade tolerance be considered for species when evaluating ecosystem functions and predicting plant responses to environmental changes., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

There is a lack of information on the compound profile of Cornus officinalis Sieb. et Zucc. seeds. This greatly affects their optimal utilization. In our preliminary study, we found that the extract of the seeds displayed a strong positive reaction to the FeCl 3 solution, indicating the presence of polyphenols. However, to date, only nine polyphenols have been isolated. In this study, HPLC-ESI-MS/MS was employed to fully reveal the polyphenol profile of the seed extracts. A total of 90 polyphenols were identified. They were classified into nine brevifolincarboxyl tannins and their derivatives, 34 ellagitannins, 21 gallotannins, and 26 phenolic acids and their derivatives. Most of these were first identified from the seeds of C. officinalis . More importantly, five new types of tannins were reported for the first time: brevifolincarboxyl-trigalloyl-hexoside, digalloyl-dehydrohexahydroxydiphenoyl (DHHDP)-hexdside, galloyl-DHHDP-hexoside, DHHDP-hexahydroxydiphenoyl(HHDP)-galloyl-gluconic acid, and peroxide product of DHHDP-trigalloylhexoside. Moreover, the total phenolic content was as high as 79,157 ± 563 mg gallic acid equivalent per 100 g in the seeds extract. The results of this study not only enrich the structure database of tannins, but also provide invaluable aid to its further utilization in industries.

The co-amorphous solid dispersion (c-ASD) is a useful method to enhance water solubility of poorly soluble drugs. The objective of this study was to improve the dissolution of Neohesperidin (NE) via binary c-ASD which, to the best of our knowledge, has not yet been reported. Since NE and Naringin (NA) co-exist abundantly in Chinese herbal medicine Fructus Aurantii Immaturus, it was hypothesised that NA served as a co-former of NE-NA c-ASD to improve the dissolution profile of NE. Hence, NA was selected to prepare c-ASD with NE at a weight ratio of 4:10, 10:10, 10:4 by lyophilisation. They were characterised according to thermal properties, molecular interactions, dissolution properties and physical stability. We found that the 10:10 ratio was the most potent in enhancing the dissolution behaviour of NE; whereby NE and NA are highly synchronous in pair-wise solvation process. A molecular mixture was achieved through the intermolecular H-bond and pi-pi stacking force formed between NE and NA and was stable for 7 -months. We concluded that the NE-NA co-amorphous binary system is a promising strategy to improve the dissolution behaviour and stabilise the amorphous state of NE. Bionic co-former selection may be an innovative and effective way to accurately determine the appropriate co-former of poorly water soluble substances., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The combined catalytic systems derived from organocatalysts and transition metals exhibit powerful activation and stereoselective-control abilities in asymmetric catalysis. This work describes a highly efficient chiral aldehyde-nickel dual catalytic system and its application for the direct asymmetric α-propargylation reaction of amino acid esters with propargylic alcohol derivatives. Various structural diversity α,α-disubstituted non-proteinogenic α-amino acid esters are produced in good-to-excellent yields and enantioselectivities. Furthermore, a stereodivergent synthesis of natural product NP25302 is achieved, and a reasonable reaction mechanism is proposed to illustrate the observed stereoselectivity based on the results of control experiments, nonlinear effect investigation, and HRMS detection., (© 2022. The Author(s).)

As a promising high mobility p-type wide bandgap semiconductor, copper iodide has received increasing attention in recent years. However, the defect physics/evolution are still controversial, and particularly the ultrafast carrier and exciton dynamics in copper iodide has rarely been investigated. Here, we study these fundamental properties for copper iodide thin films by a synergistic approach employing a combination of analytical techniques. Steady-state photoluminescence spectra reveal that the emission at ~420 nm arises from the recombination of electrons with neutral copper vacancies. The photogenerated carrier density dependent ultrafast physical processes are elucidated with using the femtosecond transient absorption spectroscopy. Both the effects of hot-phonon bottleneck and the Auger heating significantly slow down the cooling rate of hot-carriers in the case of high excitation density. The effect of defects on the carrier recombination and the two-photon induced ultrafast carrier dynamics are also investigated. These findings are crucial to the optoelectronic applications of copper iodide., (© 2022. The Author(s).)

Objective: Arginine ADP-ribosyltransferase 1 (ART1) is involved in the regulation of a diverse array of pathophysiological processes, including proliferation, invasion, apoptosis, autophagy and angiogenesis of colorectal cancer (CRC) cells. However, how ART1 regulates glycolysis in CRC remains elusive., Methods: To elucidate the role of ART1 in glycolysis in CRC, we assessed the protein level of ART1, hypoxia-inducible factor 1α (HIF1α), and glucose transporter type 1 (GLUT1) in 61 CRC tumor tissue specimens obtained from patients with different 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 F-FDG) uptake as analyzed by PET/CT before surgery. Colon adenocarcinoma CT26 cells with ART1 knockdown and overexpression were established, respectively, and the molecular mechanism underlying the effect of ART1 on glycolysis in CRC was determined both in vivo and in vitro., Results: The expression of ART1 and GLUT1 was significantly associated with FDG uptake (P=0.037 and P=0.022, respectively) in CRC tissues. Furthermore, the expression of hexokinase 2 (HK2) and lactate dehydrogenase (LDH) was upregulated in ART1-overexpressed CT26 cells, but was downregulated in ART1-knockdown CT26 cells. The volume and weight of subcutaneously transplanted tumors were markedly increased in the ART1-overexpressed BALB/c mice group and decreased in the ART1-knockdown group. In CT26 cells, the overexpression of ART1 promoted the expression levels of HK2 and LDH, and knockdown of ART1 suppressed them in the CT26 tumors. In both normal and hypoxic conditions, ART1 expression was associated with the protein level of phospho-serine/threonine kinase (p-AKT), HIF1α, and GLUT1 but not with that of AKT in CT26 cells and subcutaneous transplanted tumors., Conclusion: ART1 plays a crucial role in the elevation of glucose consumption in CT26 cells and may regulate GLUT1-dependent glycolysis in CRC via the PI3K/AKT/HIF1α pathway., (© 2022. The Author(s).)

Catalytic asymmetric Tsuji-Trost benzylation is a promising strategy for the preparation of chiral benzylic compounds. However, only a few such transformations with both good yields and enantioselectivities have been achieved since this reaction was first reported in 1992, and its use in current organic synthesis is restricted. In this work, we use N-unprotected amino acid esters as nucleophiles in reactions with benzyl alcohol derivatives. A ternary catalyst comprising a chiral aldehyde, a palladium species, and a Lewis acid is used to promote the reaction. Both mono- and polycyclic benzyl alcohols are excellent benzylation reagents. Various unnatural optically active α-benzyl amino acids are produced in good-to-excellent yields and with good-to-excellent enantioselectivities. This catalytic asymmetric method is used for the formal synthesis of two somatostatin mimetics and the proposed structure of natural product hypoestestatin 1. A mechanism that plausibly explains the stereoselective control is proposed., (© 2022. The Author(s).)

Chiral α-amino ketones are common structural motifs in natural products and pharmaceuticals, as well as important synthons in organic synthesis. Thus, establishing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein we disclose a new catalytic asymmetric approach for the synthesis of chiral α-amino ketones through a chiral palladium-catalyzed arylation reaction of in situ generated challenging α-keto imines from previously unreported C -acyl N -sulfonyl- N , O -aminals, with arylboronic acids. The current reaction offers a straightforward approach to the asymmetric synthesis of acyclic α-amino ketones in a practical and highly stereocontrolled manner. Meanwhile, the multiple roles of the chiral Pd(ii) complex catalyst in the reaction were also reported., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We report on an investigation of the temperature-dependent ordering of the hydrogen/deuterium atoms in geometrically frustrated magnets Co 2 (OH) 3 Br and its deuterated Co 2 (OD) 3 Br, to shed light on the origin of the newly-identified ferroelectricity using Raman spectroscopy. Significant changes in the Raman frequencies and line-widths of the Raman-active modes were observed below ∼260 K in Co 2 (OD) 3 Br and ∼240 K in Co 2 (OH) 3 Br, respectively, the analysis of which revealed strong spin-phonon couplings in this system. Further, for Co 2 (OD) 3 Br, six new phonon bands appeared below around 260 K, with the corresponding intensities obeying a power-law equationI∝1-T/Tc2βwherein T c = 260 K, suggesting that an ordering process occurred below ∼260 K. The ordering process subsequently affected the local structure and brought out the reported ferroelectric phase, which is considered as frustrated. Meanwhile, in Co 2 (OH) 3 Br, only one new band was observed below ∼240 K, followed by two 'softened' modes correlated to the [OH] sub-lattice below ∼185 K, wherein an incomplete ordering was suggested. The present work reveals a new multiferroic system combining geometrically frustrated magnetism and deuterium ordering-type ferroelectricity., (© 2021 IOP Publishing Ltd.)

A ternary catalytic system comprising a chiral aldehyde, a transition metal, and a Lewis acid is rationally designed for the asymmetric α-allylic alkylation reaction of aza-aryl methylamines and π-allylmetal electrophiles. Structural diversity chiral amines bearing carbon-carbon double bonds and aza-heterocycles are produced in moderate to good yields with good to excellent enantioselectivities. These products can be readily converted into other chiral amines without the loss of enantioselectivity. A reasonable reaction mechanism is proposed to illustrate the stereoselective control results.

Aims: Dendrobine is a major alkaloid present mainly in dendrobium nobile Lindl. It has been reported to have analgesic, antipyretic, lower heart rate and blood pressure and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear., Methods: In this study, the in vivo metabolite profiling of dendrobine in rats was investigated using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). The metabolites were predicted using MetabolitePilotTM software with a mass defect filter (MDF) technique. These predicted metabolites were further analyzed by MS 2 spectra and compared with the detailed fragmentation pathway of the dendrobine standard and literature data., Results: Total of 59 metabolites were identified for the first time in rat plasma and urine after oral administration of dendrobine. Demethylated, dehydrogenated, hydroxylated, ketonizated and glucuronide were the major metabolic pathways., Conclusion: This research provides scientific and reliable support for full understanding of the metabolic fate of dendrobine in vivo., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Chiral aldehyde catalysis is a burgeoning strategy for the catalytic asymmetric α-functionalization of aminomethyl compounds. However, the reaction types are limited and to date include no examples of stereodivergent catalysis. In this work, we disclose two chiral aldehyde-catalysed diastereodivergent reactions: a 1,6-conjugate addition of amino acids to para-quinone methides and a bio-inspired Mannich reaction of pyridinylmethanamines and imines. Both the syn- and anti-products of these two reactions can be obtained in moderate to high yields, diastereo- and enantioselectivities. Four potential reaction models produced by DFT calculations are proposed to explain the observed stereoselective control. Our work shows that chiral aldehyde catalysis based on a reversible imine formation principle is applicable for the α-functionalization of both amino acids and aryl methylamines, and holds potential to promote a range of asymmetric transformations diastereoselectively.

MYB transcription factors (TFs) play important roles in the plant's response to abiotic stress. In this study, we cloned a novel MYB TF gene from Vaccinium corymbosum (blueberry) using rapid amplification of cDNA ends (RACE). The cDNA contained a 798-bp open reading frame that encodes a 265-amino acid protein. VcMYB4a possessed a C2/EAR-repressor motif domain and phylogenetic analysis showed that it clustered into a subgroup 4 with six Arabidopsis thaliana MYBs. Quantitative RT-PCR analysis demonstrated that VcMYB4a expression was downregulated by salt, drought, and cold treatment, but was induced by freezing and heat. Overexpression of VcMYB4a in blueberry callus enhanced sensitivity to salt, drought, cold, freezing, and heat stress. These results indicate that VcMYB4a may be an important repressor of abiotic stress in blueberry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Moesin-ezrin-radixin-like protein (Merlin) has been identified as a tumor suppressor in several types of cancers. However, the biological function of Merlin in osteosarcoma remains unclear. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we sought to evaluate the regulation of Merlin expression by miR-25-3p and the role of the miR-25-3p/Merlin axis in osteosarcoma progression, with the aim of identifying a potential therapeutic target for osteosarcoma., Materials and Methods: TCGA (The Cancer Genome Atlas) database was used to analyze the correlation between Merlin expression and prognosis. RT-qPCR and Western blotting analyses were performed to compare Merlin expression between normal and malignant cells. A dual-luciferase reporter assay was performed to evaluate the direct targeting of Merlin by miR-25-3p. We overexpressed miR-25-3p, or/and Merlin, in U-2 OS and 143B cells, and studied their cellular functions in vitro. MTT and colony formation assays were performed to determine the effects on cell growth. EdU and cell cycle assays were performed to analyze the effects in cell replication. We used annexin V-fluorescein isothiocyanate and propidium iodide to stain apoptotic cells, and analyzed the cells using flow cytometry. The effects on cell metastasis were studied in wound healing and transwell assays. Lastly, the underlying mechanism was determined in RT-qPCR and Western blotting experiments., Results: Low Merlin expression was linked to poor prognosis. miR-25-3p was observed to directly target Merlin and downregulate its expression. miR-25-3p promoted cell growth, migration, and invasion, and inhibited apoptosis induced by cisplatin. Moreover, the overexpression of Merlin reversed the abovementioned effects of miR-25-3p. Further, the miR-25-3p/Merlin axis was observed to play an important role in the Hippo pathway, and regulated the expression of genes such as BIRC5, CTGF, and CYR61., Conclusion: miR-25-3p functions as an oncogenic microRNA in osteosarcoma by targeting Merlin, and may serve as a potential therapeutic target for osteosarcoma., Competing Interests: The authors declare that they have no conflicts of interest for this work., (© 2020 Rao et al.)

A highly efficient quinine-derived primary-amine-catalyzed asymmetric aldol addition of hydroxyacetone to arylglyoxals is described. Structurally diverse anti -2,3-dihydroxy-1,4-diones were generated in high yields, with good diastereoselectivities and enantioselectivities.

The first catalytic asymmetric alkenylation of isatin imines is described. The reaction, which is promoted by a chiral bis(oxazoline)-copper complex, gives structurally diverse 3-alkenyl-3-aminooxindole derivatives in excellent yields, and with excellent diastereoselectivities and high-to-excellent enantioselectivities. The products can be readily converted to polycyclic indole derivatives without loss of enantioselectivity. A plausible chirality-induced mechanism is proposed to explain the observed stereoselective control.

A chiral aldehyde is rationally combined with a Lewis acid and a transition metal for the first time to form a triple catalytic system. This cocatalytic system exhibits good catalytic activation and stereoselective-control abilities in the asymmetric α-allylation reaction of N-unprotected amino acid esters and allyl acetates. Optically active α,α-disubstituted α-amino acids (α-AAs) are generated in good yields (up to 87%) and enantioselectivities (up to 96% ee). Preliminary mechanism investigation indicates that the chiral aldehyde 3f acts both as an organocatalyst to activate the amino acid ester via the formation of a Schiff base, and as a ligand to facilitate the nucleophilic attack process by coordinating with π-allyl Pd(II) species.

The first catalytic asymmetric Diels-Alder reaction of 3-vinylindole and nitroolefin is described. In the promotion of organocatalyst 3j, structurally diverse 1-nitro-hydrocarbazoles are produced in moderate-to-good yields and high-to-excellent enantioselectivities. All of these products are obtained as a single diastereoisomer. The 1-nitro-hydrocarbazole compounds can be converted into 1-amino-hydrocarbazole derivatives and structurally complex ring-fused indoles enantioseletively. Possible transition states were investigated by control experiments and DFT calculations.

Chiral aldehyde catalysis is uniquely suitable for the direct asymmetric α-functionalization of N-unprotected amino acids, because aldehydes can reversibly form imines. However, there have been few successful reports of these transformations. In fact, only chiral aldehyde catalyzed aldol reactions of amino acids and alkylation of 2-amino malonates have been reported with good chiral induction. Here, we report a novel type of chiral aldehyde catalyst based on face control of the enolate intermediates. The resulting chiral aldehyde is the first efficient nonpyridoxal-dependent catalyst that can promote the direct asymmetric α-functionalization of N-unprotected glycine esters. Possible transition states and the proton transfer process were investigated by density functional theory calculations.

Single-wall carbon nanotubes (SWCNTs) are ideal for fabricating transparent conductive films because of their small diameter, good optical and electrical properties, and excellent flexibility. However, a high intertube Schottky junction resistance, together with the existence of aggregated bundles of SWCNTs, leads to a degraded optoelectronic performance of the films. We report a network of isolated SWCNTs prepared by an injection floating catalyst chemical vapor deposition method, in which crossed SWCNTs are welded together by graphitic carbon. Pristine SWCNT films show a record low sheet resistance of 41 ohm □ -1 at 90% transmittance for 550-nm light. After HNO 3 treatment, the sheet resistance further decreases to 25 ohm □ -1 . Organic light-emitting diodes using this SWCNT film as anodes demonstrate a low turn-on voltage of 2.5 V, a high current efficiency of 75 cd A -1 , and excellent flexibility. Investigation of isolated SWCNT-based field-effect transistors shows that the carbon-welded joints convert the Schottky contacts between metallic and semiconducting SWCNTs into near-ohmic ones, which significantly improves the conductivity of the transparent SWCNT network. Our work provides a new avenue of assembling individual SWCNTs into macroscopic thin films, which demonstrate great potential for use as transparent electrodes in various flexible electronics.

A highly efficient alkenylation reaction of arylglyoxals with 3-vinylindoles catalyzed by chiral calcium phosphate is described. Structurally diverse allylic alcohols bearing indole and carbonyl units are prepared in excellent yields, good diastereoselectivities, and high to excellent enantioselectivities. These products are good building blocks for the synthesis of polysubstituted chiral tetrahydrocarbozol-2-ones. The mechanism study indicates that the most likely role of the catalyst is to activate the hydrate of arylglyoxal and control the stereoselectivity via desymmetric coordination.

A simple Brønsted acid catalyzed tandem reaction, including intermolecular nucleophilic addition, substitution and intramolecular cyclization, in a one-pot manner is described. Thirty two 2-indolyl substituted carbazoles are generated in good to excellent yields. Based on this tandem reaction strategy, the poly(1,4-carbazole) is prepared for the first time. Preliminary studies indicate that the poly(1,4-carbazole) has good thermostability and optical properties.

The 3-vinyl indole is used as a nucleophile to react with aromatic and aliphatic imines. Chiral 3-substituted indoles bearing multiple functional groups are produced with up to 99% yield, a 98:2 E/Z ratio, and 97% ee. A possible mechanism is proposed to explain the observed stereoselectivities. This strategy provides an efficient way for the preparation of novel chiral 3-substituted indoles.

Organic light-emitting diodes (OLEDs) are driven by injected charges from an anode and a cathode. The low and high work function metals are necessary for the effective injection of electrons and holes, respectively. Here, we introduce a fully novel design concept using organic semiconductor heterojunctions (OSHJs) as the charge injectors for achieving highly efficient OLEDs, regardless of the work functions of the electrodes. In contrast to traditional injected charges from the electrodes, the injected charges originate from the OSHJs. The device performance was shown to be significantly improved in efficiency and stability compared to conventional OLEDs. Attractively, the OLEDs based on OSHJs as charge injectors still exhibited an impressive performance when the low work function Al was replaced by air- and chemistry-stable high work function metals, such as Au, Ag, and Cu, as the cathode contact, which has been suggested to be difficult in conventional OLEDs. This concept challenges the conventional design approach for the injection of charges and allows for the realization of practical applications of OLEDs with respect to high efficiency, selectable electrodes, and a long lifetime.

To investigate the effects of TGF-β1 on the proliferation and apoptosis of cervical cancer Hela cells in vitro. Human cervical cancer Hela cells were cultured in vitro and divided into the experimental and control groups. In the experimental groups, Hela cells were stimulated with different concentrations of TGF-β1 (0.01, 0.1, 1, and 10 ng/mL), while Hela cells cultured in serum-free medium without TGF-β1 were used as controls. The CCK8 method was adopted to detect the effect of TGF-β1 on Hela cell proliferation, and flow cytometry was used to determine cell apoptosis 72 h after TGF-β1 treatment. Compared with the control group, the CCK-8 tests showed that different concentrations of TGF-β1 had no obvious effect on Hela cell proliferation 24 h after treatment (P > 0.05). However, upon 48 or 72 h of treatment, TGF-β1 significantly inhibited the proliferation of Hela cells in a time- and dose-dependent manner (P < 0.05). The flow cytometry results indicated that TGF-β1 influenced the apoptosis of human cervical cancer Hela cells in a dose-dependent manner after 72 h of treatment (P < 0.05). TGF-β1 significantly inhibited the growth and induced the apoptosis of human cervical Hela cells in vitro.

Rapid and catalyst-free hydrazone ligation reaction between ortho-halobenzaldehyde derivatives and peptide/protein hydrazides was observed at neutral pH and room temperature. 2-Chlorobenzaldehyde exhibited the fastest reaction and highest conversion rates among the series of ortho-halobenzaldehydes. The resulting hydrazone-containing bioconjugation products were also found to be fairly stable under experimental conditions. The new ligation strategy was successfully used for protein C-terminal labeling and should provide a practical approach for the modification of proteins.

The highly efficient, regioselective, and enantioselective transfer hydrogenation of α-keto ketimines and reductive amination of diketones by Brønsted acid catalysis is described. A series of chiral α-amino ketones is prepared in high yields (up to >99%), excellent regioselectivities (up to >99:1), and enantioselectivities (up to 98% ee). This method has broad substrate scope.

An alternative stapling strategy is described herein using Fmoc-solid phase peptide synthesis (SPPS) that employed pre-prepared diaminodiacid building blocks to introduce all-hydrocarbon staples into peptides by on-resin cyclization. Compared to unstapled native peptides, diaminodiacid-based stapled peptides exhibited an increased α-helicity ratio and stability toward protease. Moreover, the linkage length was found to affect the bioactivity of the peptides and their ability to inhibit the Wnt pathway. Therefore, the new stapling method provides an alternative way to obtain stapled peptides with tunable linkers of diaminodiacids.

In this work, we describe an accelerated solid-phase synthetic protocol for ordinary or difficult peptides involving air-bath heating and amide protection. For the Hmsb-based backbone amide protection, an optimized acyl shift condition using 1,4-dioxane was discovered. The efficiency and robustness of the protocol was validated in the course of preparation of classical difficult peptides and ubiquitin protein segments.

This work describes an efficient α-alkylation reaction of α-amino aldehydes with 3-indolylmethanols. In the promotion of catalyst 3f, the target products were obtained in high yields (up to 99%), good diastereoselectivities (up to 88:12), and excellent enantioselectivities (up to 96% ee). The direct alkylation products can be readily converted into other tryptophan derivatives without the loss of stereoselectivities.

Objective: To investigate the effects of mTOR-STAT3 pathway on the invasion and migration of hepatoma cell., Methods: mTOR and STAT3 expression in the hepatocellular carcinoma cell line HepG2 and normal liver cell line L02 were detected by reverse transcription PCR (RT-PCR) and western blotting. The migration and invasion abilities of cells and expression of STAT3 were detected by scratch adhesion test and transwell migration assays, after siRNA transfection blocking mTOR expression of HepG2 cells., Results: The HepG2 cells expression is higher compared with normal cells L02 expression. Western blotting assay showed the mTOR expression was blocked, while STAT3 expression was also decreased, after the siRNA transfection of HepG2 cells. The migration (scratch adhesion test) and invasion (transwell assays) abilities of HepG2 cells which the mTOR expression was blocked by siRNA interference were significantly decreased (P<0.05)., Conclusion: mTORSTAT3 expression in hepatoma cells HepG2 was significantly higher than that in normal liver cells. mTOR blocking can reduce the expression of STAT3, which is also closely related to the invasion and metastasis of liver cancer cells., (Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)

The development of new catalytic systems for the conversion of biomass-derived molecules into liquid fuels has attracted much attention. We propose a non-noble bimetallic catalyst based on nickel-tungsten carbide for the conversion of the platform molecules 5-(hydroxymethyl)furfural into the liquid-fuel molecule 2,5-dimethylfuran (DMF). Different catalysts, metal ratios and reaction conditions have been tested and give rise to a 96% yield of DMF. The catalysts have been characterized and are discussed. The reaction mechanism is also explored through capture of reaction intermediates. The analysis of the reaction mixture over different catalysts is presented and helps to understand the role of nickel and tungsten carbide during the reaction., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Catalytic pyrolysis of 5-Hydroxymethylfurfural (HMF) was conducted on a fixed bed reactor at atmospheric pressure. HMF could be converted into aromatic hydrocarbons through catalytic pyrolysis. The catalysts and reaction conditions were both critical in maximizing the aromatic hydrocarbons selectivity. Four catalysts, β-zeolite, HZSM-5, Ga/HZSM and In/HZSM were tested in this study. HZSM-5 (Si/Al=50) was found to be the most effective catalyst in both reactivity and selectivity among these catalysts. Under the reaction temperature of 600 °C, the highest carbon yield of 48.99% of aromatic hydrocarbons was achieved from catalytic pyrolysis HMF with HZSM-5 (Si/Al=50) as catalyst. Moreover, the HZSM-5 (Si/Al=50) catalyst was recycled for five times without shown deactivation of the catalyst., (Copyright © 2013. Published by Elsevier Ltd.)