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A synthetic method for the preparation of 1,8-dihydroindeno[2,1-b]pyrroles and pyrrol-2-yl methanols in an enantioselective manner that relies on the chiral gold(I)-catalysed reactions of β-amino-1,4-enynols is described. A divergence in product selectivity was achieved by exploiting the electrostatic interactions between the chiral counteranion of the metal catalyst and the substrate. With a gold(I) complex containing a chiral N-triflyl phosphoramide-based counteranion, tandem dehydrative Nazarov-type electrocyclisation/hydroamination of the substrate was found to selectively occur to afford the indeno-fused pyrrole adduct. In contrast, changing to a chiral phosphate-based counteranion was observed to result in a hydroamination/enantioselective formal 1,3-allylic alcohol isomerisation cascade pathway to give the 1H-pyrrole derivative.

Organochlorides are widespread in natural products, therefore the methods for site-selective chlorination at specific C–H bonds are of great interest. Here, the authors report a copper(I)-catalysed synthetic method for the efficient site-selective C(sp 3)–H bond chlorination of ketones, (E)-enones and alkylbenzenes by dichloramine-T at room temperature.

Abstract Silicon nanowire (SiNW) field-effect transistors (FETs) is a powerful tool in genetic molecule analysis because of their high sensitivity, short detection time, and label-free detection. In nucleic acid detection, GC-rich nucleic acid sequences form self- and cross-dimers and stem-loop structures, which can easily obtain data containing signals from nonspecific DNA binding. The features of GC-rich nucleic acid sequences cause inaccuracies in nucleic acid detection and hinder the development of precision medicine. To improve the inaccurate detection results, we used phosphate-methylated (neutral) nucleotides to synthesize the neutralized chimeric DNA oligomer probe. The probe fragment originated from a primer for the detection of hepatitis C virus (HCV) genotype 3b, and single-mismatched and perfect-matched targets were designed for single nucleotide polymorphisms (SNP) detection on the SiNW FET device. Experimental results revealed that the HCV-3b chimeric neutralized DNA (nDNA) probe exhibited better performance for SNP discrimination in 10 mM bis-tris propane buffer at 25 °C than a regular DNA probe. The SNP discrimination of the nDNA probe could be further improved at 40 °C on the FET device. Consequently, the neutralized chimeric DNA probe could successfully distinguish SNP in the detection of GC-rich target sequences under optimal operating conditions on the SiNW FET device.

We report in this study the identification of a natural product-like antagonist (1a) of Vps34 as a potent autophagy modulator via structure-based virtual screening. Aurone derivative 1a strongly inhibited Vps34 activity in cell-free and cell-based assays. Significantly, 1a prevents autophagy in human cells induced either by starvation or by an mTOR inhibitor. In silico modeling and kinetic data revealed that 1a could function as an ATP-competitive inhibitor of Vps34. Moreover, it suppressed autophagy in vivo and without inducing heart or liver damage in mice. 1a could be utilized as a new motif for more selective and efficacious antagonists of Vps34 for the potential treatment of autophagy-related human diseases. KEY WORDS: Autophagy, Natural products, Vps34, Inhibitor, Structure-based virtual screening, Vesicle trafficking, Heart or liver damage, Aurone derivative

Abstract Neutral DNA analogs as probes for the detection of target oligomers on the biosensors based on the field-effect transistor (FET) configuration feature advantages in the enhancement of sensitivity and signal-to-noise ratio. Herein, we used phosphate-methylated nucleotides to synthesize two partially neutralized chimeric DNA products and a fully neutralized DNA sequence and adopted a regular DNA oligomer as probes on the polycrystalline silicon nanowire (NW) FET devices. The sequences of two neutralized chimeric DNAs close to the 5′ end were alternately modified with the phosphate-methylated nucleotides, and all probes were immobilized via their 5′ end on the NW surface. The non-specific-to-specific binding ratio indicated that the two 5′-end partially neutralized chimeric DNAs featured better performance than the regular and fully neutralized DNA oligomers. The partially neutralized probe design reduces the ionic strength needed for hybridization and increases the Debye length of detection, thus promoting the detection sensitivity of FET and achieving the limit of detection of 0.1 fM. By using an appropriate probe design, applying DNA oligomers with embedded phosphate-methylated nucleotides in the FET biosensors is a promising way for gene detection with high sensitivity and specificity.

Detecting proteins at low concentrations in high-ionic-strength conditions by silicon nanowire field-effect transistors (SiNWFETs) is severely hindered due to the weakened signal, primarily caused by screening effects. In this study, aptamer as a signal amplifier, which has already been reported by our group, is integrated into SiNWFET immunosensors employing antigen-binding fragments (Fab) as the receptors to improve its detection limit for the first time. The Fab-SiNWFET immunosensors were developed by immobilizing Fab onto Si surfaces modified with either 3-aminopropyltriethoxysilane (APTES) and glutaraldehyde (GA) (Fab/APTES-SiNWFETs), or mixed self-assembled monolayers (mSAMs) of polyethylene glycol (PEG) and GA (Fab/PEG-SiNWFETs), to detect the rabbit IgG at different concentrations in a high-ionic-strength environment (150 mM Bis-Tris Propane) followed by incubation with R18, an aptamer which can specifically target rabbit IgG, for signal enhancement. Empirical results revealed that the signal produced by the sensors with Fab probes was greatly enhanced compared to the ones with whole antibody (Wab) after detecting similar concentrations of rabbit IgG. The Fab/PEG-SiNWFET immunosensors exhibited an especially improved limit of detection to determine the IgG level down to 1 pg/mL, which has not been achieved by the Wab/PEG-SiNWFET immunosensors.

A one-pot, two-step approach to prepare 2-tetrahydrofuran and -pyran substituted 1,3-dicarbonyl compounds by PhI=NTs-mediated amination/Brønsted base-catalyzed cross dehydrogenative coupling (CDC) reaction of the cyclic ether and 1,3-dicarbonyl derivative under mild conditions is reported. The reaction is compatible with a variety of cyclic ethers and 1,3-dicarbonyl compounds, affording the corresponding coupled products in moderate to good yields of up to 80% over two steps.

We report herein the use of an exonuclease III and G-quadruplex probe to construct a G-quadruplex-based luminescence detection platform for Hg2+. Unlike common DNA-based Hg2+ detection methods, when using the dsDNA probe to monitor the hairpin formation, the intercalation of the dsDNA probe may be influenced by the distortion of dsDNA. This ‘mix-and-detect’ methodology utilized the G-quadruplex probe as the signal transducer and is simple, rapid, convenient to use and can detect down to 20 nM of Hg2+.

The molecule of the title compound, C25H24O, obtained by acid-catalysed 1,3-migration of an alcohol group, is T-shaped. The planes of the two phenyl rings are inclined to one another by 81.9 (2)°. In the crystal, molecules are linked by O—H...O hydrogen bonds, forming chains along [001].

In this study, we applied structure-based virtual screening techniques to identify natural product or natural product-like inhibitors of iNOS. The iNOS inhibitory activity of the hit compounds was characterized using cellular assays and an in vivo zebrafish larvae model. The natural product-like compound 1 inhibited NO production in LPS-stimulated Raw264.7 macrophages, without exerting cytotoxic effects on the cells. Significantly, compound 1 was able to reverse MPTP-induced locomotion deficiency and neurotoxicity in an in vivo zebrafish larval model. Hence, compound 1 could be considered as a scaffold for the further development of iNOS inhibitors for potential anti-inflammatory or anti-neurodegenerative applications.

The syntheses and reactivities of sterically encumbered trans-dioxoosmium(VI) complexes containing Schiff-base ligands bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-diamine (H2(super t)Bu-salch) and bis(3,5-dibromosalicylidene)-1,2-cyclohexane-diamine (H2BR-salch) are described. Product formation is shown to occur more quickly for reactions derived from alkenes substituted with an electron-donating group compared to those derived from electron-withdrawing substituted alkenes.

A study on tandem sulfonium/ammonium ylide formation/[2,3]-sigmatropic rearrangement reactions through ruthenium porphyrin catalyzed decomposition of diazo compounds in the presence of allyl sulfides and amines is reported noting the synthetic value of reactive ylides. A concise synthesis of a natural alkaloid (plusmn)-platynecine is also presented.

A synthetic method that enables the Hantzsch ester‐mediated Minisci‐type C2‐alkylation of quinolines, isoquinolines and pyridines by N‐(acyloxy)phthalimide esters (NHPI) under blue LED (light emitting diode) light (456 nm) is described. Achieved under mild reaction conditions at room temperature, the metal‐free synthetic protocol was shown to be applicable to primary, secondary and tertiary NHPIs to give the alkylated N‐heterocyclic products in yields of 21–99%. On introducing a chiral phosphoric acid, an asymmetric version of the reaction was also realised and provided product enantiomeric excess (ee) values of 53–99%. The reaction mechanism was delineated to involve excitation of an electron‐donor acceptor (EDA) complex, formed from weak electrostatic interactions between the Hantzsch ester and NHPI, which generates the posited radical species of the redox active ester that undergoes addition to the N‐heterocycle. [ABSTRACT FROM AUTHOR]

Heat treatment of a solution of MeOH and water is described containing the quitenine HQA {HQA = 6-methoxy-(8S-9R)-cinchonan-9-ol-3-carboxylic acid} and Zn[Cl.sub.2] at 70 degrees C to give the one-dimensional (1D) chain coordination polymer {(HQA)(Zn[Cl.sub.2])(2.5[H.sub.2]O)}[.sub.n]. Measurements of its dielectric properties showed that the 1D chain coordination polymer exhibited a dipolar chain relaxation process and a high dielectric constant.

A general and efficient method is described for preparing 2,4-di- and trisubstituted thiazoles through p-TsOH.[H.sub.2]O-catalyzed cyclization of trisubstituted propargylic alcohols with thioamides. The reaction is achieved in under mild conditions that has not required the exclusion of air and moisture and has provided a convenient route to the synthetically useful aromatic heterocycle.

An efficient synthetic route to 1,2-dihydroquinolines that relies on Au[Cl.sub.3]/AgSb[F.sub.6]-catalyzed intramolecular allylic amination of 2-tosylaminophenylprop-1-en-3-ols is described. The N-heterocyclic ring forming strategy as a synthetic tool that involved activation of the alcohol substrate as pro-electrophiles could find application for synthesis of wide range of the bioactive tetrahydroquinoline alkaloid (plusminus)-angustureine.

Anisotropic permittivity measurements are performed on a novel homochiral trinuclear nickel(II) complex. These metal complexes have displayed huge and stable dielectric anisotropic effect with temperature-independent property.

The syntheses and luminescent properties of three novel zinc coordination polymers containing tetrazolyl ligands are described. By employing the in situ Demko-Sharpless [2+3] cycloaddition synthesis, reactions of acetonitrile or p-tolylnitrile with sodium azide in the presence of zinc perchlorate as a Lewis acid under hydrothermal condition gave [Zn(CH3CN4)2]3(H2O) and [Zn(4-MPTZ)2] in good yields.

This short review aims to summarize how the product outcome of reactions of a common starting material can sometimes be controlled by the judicious choice of copper, silver or gold as the catalyst. It highlights the different reactivities observed in the functional group transformations of π-rich substrates mediated by the three group 11 metal salts. 1 Introduction 2 Reactions of Propargyl Amines, Esters and Their Derivatives 3 Reactions of Phenylacetylene Derivatives 4 Reactions of π-Rich Alcohols and Ethers 5 Indolyl Cyclopropene and Alkynone Rearrangements 6 Reactions Involving Metal-Carbene and Metal-Carbenoid Intermediates 7 Conclusion. [ABSTRACT FROM AUTHOR]

The synthesis of α,α-diacylaziridines and α,α,β-triacylaziridines from reaction of 2-alkyl-substituted-1,3-dicarbonyl compounds and 2-acyl-substituted-1,4-dicarbonyl compounds with arylsulfonyliminoiodinanes (ArSO2N = IPh) under Brønsted base-mediated atmospheric conditions is described. The reaction mechanism is thought to involve the formal oxidation of the substrate followed by aziridination of the ensuing α,β-unsaturated intermediate by the hypervalent iodine(III) reagent. [ABSTRACT FROM AUTHOR]

A one-pot, two-step approach to prepare 2-tetrahydrofuran and -pyran substituted 1,3-dicarbonyl compounds by PhI=NTs-mediated amination/Brønsted base-catalyzed cross dehydrogenative coupling (CDC) reaction of the cyclic ether and 1,3-dicarbonyl derivative under mild conditions is reported. The reaction is compatible with a variety of cyclic ethers and 1,3-dicarbonyl compounds, affording the corresponding coupled products in moderate to good yields of up to 80% over two steps. [ABSTRACT FROM AUTHOR]

One of the major challenges faced in modern synthetic chemistry is the efficient and selective assembly of complex molecular structures, especially carbo- and heterocycles, from readily accessible starting materials. With this has arisen the development of tandem reaction processes, which permit multiple transformations in a single synthetic step and that have often provided elegant routes to complex target scaffolds from simple precursors. Propargyl alcohols and their derivatives have become increasingly attractive starting materials for such processes owing to their reactivity in the presence of a Brønsted or Lewis acid catalyst as well as halogenation reagents. This account describes our recent efforts in the field, and demonstrates how propargyl alcohols and their derivatives can be transformed into a diverse range of highly functionalized acyclic, carbocyclic and heterocyclic structures, which are of importance as synthetic building blocks and as motifs in functional materials and bioactive compounds. 1 Introduction 2 Acyclic Conjugated Enynes 3 Carbocycles 3.1 Indenes 3.2 Dihydrofluorenes 3.3 Cyclopentenes, Cyclobutenes and Cyclopenta[b]naphthalenes 3.4 ortho-Phenolic Esters 4 Heterocycles with One Heteroatom 4.1 Indoles 4.2 Piperidines, Azepines and Pyrrolidines 4.3 Pyrroles 4.4 Furans 4.5 Benzo[b]oxepines and Benzo[b]azepines 5 Heterocycles with Two Heteroatoms 5.1 Thiazoles and Oxazoles 5.2 Dioxolanes 6 Conclusion [ABSTRACT FROM AUTHOR]

We present in this article an external memory algorithm, called disk SA-IS (DSA-IS), to exactly emulate the induced sorting algorithm SA-IS previously proposed for sorting suffixes in RAM. DSA-IS is a new disk-friendly method for sequentially retrieving the preceding character of a sorted suffix to induce the order of the preceding suffix. For a size-n string of a constant or integer alphabet, given the RAM capacity Ω((nW)0.5), where W is the size of each I/O buffer that is large enough to amortize the overhead of each access to disk, both the CPU time and peak disk use of DSA-IS are O(n). Our experimental study shows that on average, DSA-IS achieves the best time and space results of all of the existing external memory algorithms based on the induced sorting principle. [ABSTRACT FROM AUTHOR]

A synthetic method to aminate 1,3-dicarbonyl compounds with PhI=NTs using Brønsted acid catalysis is described herein. The method was shown to be applicable to β-keto esters and phosphonates as well as 1,3-diones, providing the corresponding α,α-acyl amino acid derivatives in moderate to excellent yields. [ABSTRACT FROM AUTHOR]

We present a new suffix array construction algorithm that aims to build, in external memory, the suffix array for an input string of length n measured in the magnitude of tens of Giga characters over a constant or integer alphabet. The core of this algorithm is adapted from the framework of the original internal memory SA-DS algorithm that samples fixed-size d-critical substrings. This new external-memory algorithm, called EM-SA-DS, uses novel cache data structures to construct a suffix array in a sequential scanning manner with good data spatial locality: data is read from or written to disk sequentially. On the assumed external-memory model with RAM capacity Ω ((nB)0.5), disk capacity O(n), and size of each I/O block B, all measured in log n-bit words, the I/O complexity of EM-SA-DS is O(n/B). This work provides a general cache-based solution that could be further exploited to develop external-memory solutions for other suffix-array-related problems, for example, computing the longest-common-prefix array, using a modern personal computer with a typical memory configuration of 4GB RAM and a single disk. [ABSTRACT FROM AUTHOR]

Due to the potential capability of providing unconditional security, arbitrated quantum signature (AQS) schemes, whose implementation depends on the participation of a trusted third party, received intense attention in the past decade. Recently, some typical AQS schemes were cryptanalyzed and improved. In this paper, we analyze the security property of some AQS schemes and show that all the previous AQS schemes, no matter whether original or improved, are still insecure in the sense that themessages and the corresponding signatures can be exchanged among different receivers, allowing the receivers to deny having accepted the signature of an appointed message. Some further improved methods on the AQS schemes are also discussed. [ABSTRACT FROM AUTHOR]