A new approach for the synthesis of triazolyl-linked α-(2-9) oligosialic acids by iterative copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC) and desilylation has been developed. By using propargyl α-sialoside 5 and trimethylsilylated-propargyl 9-azido-α-sialoside 3 as building blocks, triazolyl-linked α-(2-9) di- to octa-sialic acids were constructed in good to moderate yields. Finally, the pseudo-α-(2-9)-oligosialic acids were obtained very smoothly via O-deprotection. The oligosialic acids with a triazolyl-linkage represent a new type of pseudooligosialic acids. This protocol may find applications in the preparation of oligosialic acid analogues with biological importance.

We have previously described the discovery of N-alkylated iminosugars that showed immunosuppressive activity both in vitro and in vivo. Herein, we report the synthesis and biological evaluation of N-arylated lactam-type iminosugar derivatives. The synthesis started from simple monosaccharides and featured a Buchwald-Hartwig coupling reaction to construct the key N-aryl connection, thereby providing a highly diverse compound library. Structure-activity relationship studies, guided by a mouse-spleen-proliferation assay, led to the identification of 'hit' compound 12 f. Subsequently, the systematic modification of compound 12 f afforded compounds 21 h, 21 k, 21 n, 21 t, and 21 x with improved activities (IC50 =12-30 μM) and low Jurkat cytotoxicities (IC50 >100 μM). These new compounds also inhibited the secretion of IFN-γ and IL-4, which are hallmark cytokines of Th1 and Th2 cells, respectively. This work demonstrated that the N-arylated iminosugar structure represents a new scaffold with immunosuppressive activity.

A novel transformation of methyl imines into α-iminonitriles under mild and transition-metal-free conditions is described. Three C sp 3-H bonds are cleaved in a radical pathway at room temperature under air. Simple bromide salts are employed to assist this radical process (see scheme; FG=functional group, PIDA = iodobenzene diacetate, TMS = trimethylsilyl).

In traditional two-dimensional(2D) NMR experiments,spectral resolution in the F1 dimension is usually higher than that in the F2 dimension.Therefore,in the HSQC experiments,the spectral resolution in the 13C dimension is lower than that in the 1H dimension.This is the opposite in the 1H,13C-COSY experiments.In this work,a method for improving the resolution of 2D NMR spectrum was presented,in which HSQC and 1H,13C-COSY spectra were overlapped,and then the weaker points were selected,saved and displayed.The method was implemented as an AU program within the Bruker Topspin framework.It was demonstrated experimentally that the method could improve spectral resolution,at no cost of signal-to-noise ratio.The method can also be used to suppress F1 noise.

In this article, the total syntheses of antimalarial compound decursivine and its biologically inactive sibling serotobenine are presented. The biomimetic synthesis of (±)-serotobenine was investigated first, but failed. During the subsequent investigation of other synthetic routes, we discovered a new cascade Witkop photocyclization/elimination/addition sequence, which enabled the expedient synthesis of not only racemic decursivine and serotobenine, but also enantiopure (+)- and (-)-decursivine and a variety of their analogues. The present syntheses represent the shortest pathway for the total synthesis of decursivine and serotobenine to date. Moreover, the newly developed cascade sequence for the total synthesis of decursivine does not need any protecting steps. The scope and the reaction mechanism of the cascade sequence were also studied. A rational mechanism for the cascade sequence is proposed, which is consistent with the previous studies and our current experimental results.

A novel growing neural gas (GNG) based the learning topology, called the flexible node insertion GNG (FNIGNG), as well as its application to hand gesture representation are introduced in this paper. Compared with the fixed node insertion policy used in the typical GNG network, our proposed network applies a flexible node insertion scheme by analyzing the network mean squared error (MSE). Experimental results show that our approach is able to shorten the training time while not impairing the training accuracy.

AbstractA novel method for the synthesis of different substituted 2‐(pyridin‐2‐yl)phenols by using the title reagents is developed.

A new approach for the hand image segmentation is presented in this paper. This method integrates the merits of histogram threshold, seeded region growing (SRG) and the Restricted Coulomb Energy (RCE) neural network. The performance of our proposed method is quantitatively compared with these three methods conducted independently. Experimental results have shown that our method is effective for the segmentation, which can be further used in the gesture-based human-computer interaction.

A novel and efficient Rh-catalyzed intermolecular C–H amination of heteroarylarenes with aryl azides has been developed. This procedure does not require an oxidant, releases N2 as the only byproduct, and provides an efficient approach to diarylamines with broad functional-group tolerance.

AbstractAn alkenylation of indoles at C‐3 is developed through tandem addition and oxidative dehydration.

A novel and efficient copper or nickel catalyzed highly selective denitrogenative annulation of vinyl azides with aryl acetaldehydes has been developed. 2,4- and 3,4-diaryl substituted pyrroles, which are difficult to synthesize by the reported methods, can be highly regioselectively prepared by this protocol simply switched by the selection of the transition metal catalysts. Compared with the reported acidic or basic conditions for polysubstituted pyrrole synthesis, the present reaction conditions are mild, neutral, and very simple without any additives.

An efficient TEMPO-catalyzed oxidative C-C bond formation with two Csp(3)-H bonds using molecular oxygen as the oxidant has been developed. The novel transformation provides a new strategy for the TEMPO-O(2) catalysis to construct C-C bonds. The advantages of this method include: (1) relatively mild and neutral conditions; (2) simplicity and safety of operation; (3) a stoichiometric amount of dangerous oxidants, any transition metals, additives, even solvent, is not required.

Simple and efficient NHC-catalyzed transformations of bromoenal or alpha,beta-dibromoenal into alpha,beta-unsaturated esters or amides with high stereoselectivity through C-O or C-N bond formation have been demonstrated. The NHC-catalyzed processes occur under mild conditions. The ready availability of the starting materials, avoidance of external oxidants and the usefulness of the products all make the strategy attractive.

In pole position: A simple and efficient approach to spirocyclic γ-lactam oxindoles by the N-heterocyclic carbene catalyzed addition of homoenloate equivalents to N-aryl isatinimines has been developed (see scheme). The use of N-aryl isatinimines as electrophiles in the NHC-catalyzed umpolung reaction of α,β-unsaturated aldehydes is demonstrated for the first time.

An efficient and convergent synthesis of the C(5)-C(18) fragment of halichomycin is reported. Butanolide fragment 6 was readily prepared stereoselectively from (R)-Roche ester through catalyst control; dienylic bromide domain 7 was synthesized from (S)-serine by substrate control. C(5)-C(18) fragment 2 was rapidly assembled through a stereoselective alkylation of the butanolide with the dienylic bromide, followed by functional group transformations.

AbstractThe title transformation, providing a simple and efficient approach to modify 9,10‐dihydroacridine derivatives at the 9 position, proceeds under mild and neutral conditions, even in the absence of solvents.

A regioselective, palladium-catalyzed domino Heck/C-H activation/intermolecular direct arylation reaction has been developed, providing rapid access to diverse biaryl heterocycles.

Photochemischer Schlüsselschritt: Kurze Totalsynthesen von (±)-Decursivin und (±)-Serotobenin nutzen die im Titel bezeichnete, biomimetische Reaktionskaskade. Die Synthese des Antimalariawirkstoffs (±)-Decursivin gelang in fünf Stufen ohne Einsatz von Schutzgruppen. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

AbstractThe copper‐promoted direct insertion of nitrogen into alkenes and simple hydrocarbon molecules results in formation of 1,5‐disubstituted tetrazoles under mild and neutral conditions.

The disturbance of the insulin-signaling pathway plays an important role in Alzheimer's disease. Resistance to insulin signaling renders neurons energy-deficient and vulnerable to oxidization or other metabolic insults and impairs synaptic plasticity. In search of neuroprotective drugs, we synthesized a peptide analogue, P165, an active domain of the soluble amyloid precursor protein, which is resistant to degradation and is suitable for oral administration in a clinical setting. Initially, we confirmed that P165 can protect cells from streptozotocin-caused damage and stimulate cell outgrowth using cultured SH-SY5Y cell lines treated with streptozotocin. P165 significantly reduced lactate dehydrogenase leakage from damaged cells, thereby rescuing cell energy production. Insulin signaling such as insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) proteins were upregulated to stimulate cell survival and growth. We proceeded to investigate the effect of P165 on streptozotocin-treated Alzheimer's disease (AD) rats. The data showed that P165 protected synaptic loss and dysfunction by increasing synaptophysin and PSD-95 (post synaptic density-95), while simultaneously decreasing α-synuclein expression. Moreover, animal behavior testing clearly showed that P165 increased rats' learning and memory activity. Overall, these results constitute evidence that peptide analogue 165 may protect synapse and improve learning and memory ability in AD.