Search

The photoinitiated intramolecular hydroetherification of alkenols has been used to form C-O bonds, but the intermolecular hydroetherification of alkenes with alcohols remains an unsolved challenge. We herein report the visible-light-promoted 2-deoxyglycosylation of alcohols with glycals. The glycosylation reaction was completed within 2 min in a high quantum yield (ϕ=28.6). This method was suitable for a wide array of substrates and displayed good reaction yields and excellent stereoselectivity. The value of this protocol was further demonstrated by the iterative synthesis of 2-deoxyglycans with α-2-deoxyglycosidic linkages up to a 20-mer in length and digoxin with β-2-deoxyglycosidic linkages. Mechanistic studies indicated that this reaction involved a glycosyl radical cation intermediate and a photoinitiated chain process.

We report a novel and highly stereoselective electro-2-deoxyglycosylation from glycals. This method features excellent stereoselectivity, scope, and functional-group tolerance. This process can also be applied to the modification of a wide range of natural products and drugs. Furthermore, a scalable synthesis of glycosylated podophyllotoxin and a one-pot trisaccharide synthesis through iterative electroglycosylations were achieved.

Highly efficient emission has been a long-lasting pursuit for carbon dots (CDs) owing to their enormous potential in optoelectronic applications. Nevertheless, their room-temperature phosphorescence (RTP) performance still largely lags behind their outstanding fluorescence emission, especially in the blue spectral region. Herein, high-efficiency blue RTP CDs have been designed and constructed via a simple molecular engineering strategy, enabling CDs with an unprecedented phosphorescence quantum efficiency of to 50.17% and a long lifetime of 2.03 s. This treating route facilitates the formation of high-density (n, π*) configurations in the CD π-π conjugate system through the introduction of abundant functional groups, which can evoke a strong spin-orbit coupling and further promote the intersystem crossing from singlet to triplet excited states and radiative recombination from triplet excited states to ground state. With blue phosphorescent CDs as triplet donors, green, red, and white afterglow composites are successfully fabricated via effective phosphorescence Förster resonance energy transfer. Importantly, the color temperature of the white afterglow emission can be widely and facilely tuned from cool white to pure white and warm white. Moreover, advanced information encryption, light illumination, and afterglow/dynamic visual display have been demonstrated when using these multicolor-emitting CD-based afterglow systems.

Summary of main observation and conclusion The N-glycans attached to some chloroviruses comprise a hyperbranched core structure without precedent. We are interested in the chemical synthesis of the hexasaccharide attached to ATCV-1 (Acanthocystis turfacea Chlorella virus 1) for its distinct structure. After exploring four routes, the target hexasaccharide 2 was successfully synthesized for the first time in overall 10% yield over 8 steps from thioglycoside building blocks. This synthetic protocol is characterized by the three-component one-pot glycosylation and the regioselective glycosylation reactions. The disclosed synthetic approach to this new type of N-glycans will facilitate the in-depth understanding of their biological functions.

The chirality of supramolecular polymeric materials is subtly affected by a delicate balance among various non-covalent interactions, the details of which are inadequately understood. Now, a fine balance of intermolecular interactions, including closed-shell metal-metal, dispersive and electrostatic interactions, is used to direct the delicate orientation of monomeric building blocks, thereby achieving the successful preparation of different nanostructures with distinct supramolecular chirality. Moreover, kinetically trapped and thermodynamically stable aggregates were monitored over time in the supramolecular polymerization of cationic PtII complexes. The dynamic self-assembly process can be successfully controlled by modifying the counteranion and solvent composition. A chiral doping approach can also be used to induce the chirality of an achiral PtII complex at the supramolecular level.

It is important to find more effective and safer immunosuppressants, because clinically used immunosuppressive agents have significant side effects. A series of N-substituted iminosugar derivatives were designed and synthesized, and their immunosuppressive effects were evaluated by the CCK-8 assay. The results revealed that iminosugars 10 e and 10 i, that is, (3R,4S)-1-(4-heptyloxylphenylethyl)pyrrolidine-3,4-diol and (3R,4S)-1-[2-(2-chloro-4-(p-tolylthio)-phenyl-1-yl)ethyl]pyrrolidine-3,4-diol, respectively, exhibited the strongest inhibitory effects on mouse splenocyte proliferation (IC50 =2.16 and 2.48 μm, respectively), whereas the iminosugars containing an amide group near the hydrophilic head (compounds 10 j-n) exhibited no inhibitory effects. Further studies revealed that the inhibitory effects on splenocyte proliferation may have come from the suppression of both IFN-γ and IL-4 cytokines. Our results suggest that synthetic iminosugars, especially compounds 10 e and 10 i, hold potential as immunosuppressive agents.

Hypertension is a main risk factor for atrial fibrillation, but the direct effects of hydrostatic pressure on the atrial fibrosis are still unknown. The present study investigated whether hydrostatic pressure is responsible for atrial fibrosis, and addressed a potential role of the Smad pathway in this pathology. Biochemical assays were used to study regulation and expression of fibrotic factors in spontaneously hypertensive rats (SHRs) and Wistar rats, and in cardiac fibroblasts (CFs) cultured under standard (0 mmHg) and elevated (20, 40 mmHg) hydrostatic pressure. Levels of atrial fibrosis and protein expression of fibrotic factors Col-1A1/-3A1, TGF-β1, and MMP-2 in SHRs' left atrial tissues were higher than those in Wistar rats. Exposure to elevated pressure was associated with the proliferation of CFs. The protein expression of Col-1A1/-3A1, TGF-β1, and MMP-2 in CFs was also up-regulated in a pressure-dependent manner. The proliferation of CFs and increased expressions of fibrotic markers induced by elevated hydrostatic pressure could be reversed by the Smad3 inhibitor naringenin. The activation of Smad3 pathway was also stimulated by elevated hydrostatic pressure. These results demonstrate that CF secretory function and proliferation can be up-regulated by exposure to elevated pressure, and that Smad3 may modulate CF activation induced by high hydrostatic pressure.

Three new iminosugar-containing KRN7000 (also referred to as α-GalCer) analogues were designed and synthesized. In the design, the galactose moiety of KRN7000 was replaced by iminosugars and the iminosugar structures were connected with ceramide in different manners with a C-glycosidic bond instead of the O-glycosidic bond. To our knowledge, this is the first report in which iminosugars are incorporated in KRN7000 structure modifications. The synthetic compounds were evaluated for their ability to stimulate cytokine release. The results may benefit better understanding of structure-activity relationships and facilitate future design of more KRN7000 derivatives.

A stereoselective Koenigs-Knorr glycosylation reaction under the catalysis of urea is described. This method is characterized by urea-mediated hydrogen-bond activation and subsequent glycosylation with glycosyl chlorides or bromides. Excellent yields and high anomeric selectivity can be achieved in most cases. Moreover, the low α-stereoselectivity of glycosylations observed when using perbenzylated glucosyl donors can be greatly improved by the addition of tri-(2,4,6-trimethoxyphenyl)phosphine (TTMPP).

An efficient method for the construction of cyclopropane-fused dihydroquinolines was established by a novel Povarov-type three-component reaction of aromatic aldehydes, anilines and cyclopropenes in the presence of trifluoromethanesulfonic acid. The reaction proceeded in a regioselective and diastereoselective manner. Furthermore, the dihy-droquinolines were smoothly converted to benzazepine derivatives via a ring opening/isomerization sequence, further expanding the synthetic scope.

Organometal halide perovskite and poly(ethylene oxide) composite thin films are studied. Single-layer light-emitting diodes using the composite thin film sandwiched between indium tin oxide and indium-gallium eutectic alloy exhibit a low turn-on voltage and high brightness because of the ionic conductivity of the composite film and the formation of a p-i-n homojunction.

Iminosugars are an extremely interesting and versatile class of compounds and have many potential therapeutic applications. However, the use of iminosugar derivatives as immunomodulating agents is an area that is less explored. This review describes recent advances in the field of iminosugars as immunomodulating agents with a particular emphasis on 1-deoxynojirimycin analogues and related compounds. Both chemical and biological aspects concerning their preparation and/or occurrence in nature, as well as their immunomodulatory properties, are discussed.

Cyclins/retinoblastoma protein (pRb) pathway participates in cardiomyocyte hypertrophy. MicroRNAs (miRNAs), the endogenous small non-coding RNAs, were recognized to play significant roles in cardiac hypertrophy. But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy. This study investigates the potential role of microRNA-16 (miR-16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy. An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC), and in a mouse with transverse aortic constriction (TAC) and in a mouse with subcutaneous injection of phenylephrine (PE) respectively. In addition, a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocyte and based on Ang-II-induced neonatal mouse ventricular cardiomyocyte respectively. We demonstrated that miR-16 expression was markedly decreased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats and mice. Overexpression of miR-16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes, and inhibition of miR-16 induced a hypertrophic phenotype in cardiomyocytes. Expressions of cyclins D1, D2 and E1, and the phosphorylated pRb were increased in hypertrophic myocardium and hypertrophic cardiomyocytes, but could be reversed by enforced expression of miR-16. Cyclins D1, D2 and E1, not pRb, were further validated to be modulated post-transcriptionally by miR-16. In addition, the signal transducer and activator of transcription-3 and c-Myc were activated during myocardial hypertrophy, and inhibitions of them prevented miR-16 attenuation. Therefore, attenuation of miR-16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2 and E1, and activating cyclin/Rb pathway, revealing that miR-16 might be a target to manage cardiac hypertrophy.

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.

Despite the fact that tissue engineered heart valves (TEHV) hold great promise for heart valve disease treatment, one of the challenges is to find suitable seeding cells. Bone marrow derived mesenchymal stem cells (MSCs) were considered to be one of the best seed cell sources. In this study we propose a novel approach to promote stem cell differentiation into the seed cells of TEHV, valvular interstitial cells (VICs). Newly induced MSCs (iMSCs) were created from a co-culture niche in which healthy human donor derived MSCs were co-cultured with cardiac fibroblasts (H9C2 cell line). Then iMSCs were transfected with either a mock vector (iMSCs(mock) ) as controls or with a vector that overexpresses thefibroblast inducible factor 14 (Fn14) gene (iMSCs(Fn14) ). Immunofluorescence staining was performed to assay VIC differentiation. Western blot analysis was performed to analyze the involved signaling pathway. The results demonstrate that the expression of α-smooth muscle actin (SMA) was significantly higher in iMSCs(Fn14) as compared with iMSC(mock) , and MSC, and also had higher co-alignment of α-actinin and stress fiber (F-actin) in bundles. Additionally, increased biosynthesis of extracellular matrix (ECM) proteins including collagen I, collagen III, and fibronection were observed in iMSCs(Fn14) in comparison with iMSCs(mock) . These data observed in iMSCs(Fn14) were in accordance with VIC phenotype from normal heart valves. In addition, the PI3K/Akt signaling pathway was activated in iMSCs(Fn14) which allowed higher Akt phosphorylation (p-Akt) levels and SMA levels, whereas, it was attenuated by LY294002 (PI3K/Akt inhibitor). These new findings of the effect of Fn14 on VIC-like cell differentiation may provide a novel therapeutic strategy for heart valve disease treatment.

A stereoselective Koenigs-Knorr glycosylation reaction under the catalysis of urea is described. This method is characterized by urea-mediated hydrogen-bond activation and subsequent glycosylation with glycosyl chlorides or bromides. Excellent yields and high anomeric selectivity can be achieved in most cases. Moreover, the low α-stereoselectivity of glycosylations observed when using perbenzylated glucosyl donors can be greatly improved by the addition of tri-(2,4,6-trimethoxyphenyl)phosphine (TTMPP).