Controllable 1,3-Bis-Functionalization of 2-Nitroglycals with High Regioselectivity and Stereoselectivity Enabled by a H-Bond Catalyst.

The selective modification of carbohydrates is significant for producing their unnatural analogues for drug discovery. C1-functionalization (glycosylation) and C1,C2-difunctionalization of carbohydrates have been well developed. In contrast, C3-functionalization or C1,C3-difunctionalization of carbohydrates remains rare. Herein, we report such processes that efficiently and stereoselectively modify carbohydrates. Specifically, we found that trifluoroethanol (TFE) could promote 1,3-bis-indolylation/pyrrolylation of 2-nitroglycals generated carbohydrate derivatives in up to 93% yield at room temperature; slightly reducing the temperature could install two different indoles at the C1- and C3-positions. Switching TFE to a bifunctional amino thiourea catalyst leads to the generation of C3 monosubstituted carbohydrates, which could also be used to construct 1,3-di-C-functionalized carbohydrates. This approach produced a range of challenging sugar derivatives (over 80 examples) with controllable and high stereoselectivity (single isomer for over 90% of the examples). The potential applications of the reaction were demonstrated by a set of transformations including the synthesis of bridged large-ring molecules and gram scale reactions. Biological activities evaluation demonstrated that three compounds exhibit a potent inhibitory effect on human cancer cells T24, HCT116, AGS, and MKN-45 with IC50 ranged from 0.695 to 3.548 µM.

Alkyl/Glycosyl Sulfoxides as Radical Precursors and Their Use in the Synthesis of Pyridine Derivatives.

We report here the use of simple and readily available alkyl sulfoxides as precursors to radicals and their application in the preparation of pyridine derivatives. We show that alkyl sulfoxides, N-methoxy pyridinium salts and fluoride anions form electron donor-acceptor (EDA) complexes in solution, which, upon visible light irradiation, undergo a radical chain process to afford various pyridine derivatives smoothly. This reaction displays broad scope with respect to both sulfoxides and N-methoxy pyridiniums. The synthetic versatility of sulfoxides as a handle in chemistry adds to their power as radical precursors. Glycosyl sulfoxides are converted to the corresponding pyridyl C-glycosides with high stereoselectivities. Computational and experimental studies provide insights into the reaction mechanism.

Evaluation of GRACE mascon solutions using in-situ geodetic data: The case of hydrologic-induced crust displacement in the Yangtze River Basin.

Since the Gravity Recovery and Climate Experiment (GRACE) satellite mission was started in 2002, a variety of spatial products have been made available to further understanding of mass redistribution in the Earth system. Two such mascon (mass concentration) solutions were developed by the Center for Space Research (CSR-M) and the NASA Jet Propulsion Laboratory (JPL-M), which offers significantly improved spatial localization and more accurate amplitude measurements of changes in recovered terrestrial Total Water Storage (TWS). However, it is difficult to validate GRACE-derived TWS mascons due to the lack of independent measurements of water storage in various forms at larger scales.In this study, we present a simple framework to evaluate GRACE mascon products based on in-situ GPS measurements from the Yangtze River Basin (YRB) in China. We found that the mascons show a more pronounced spatial difference in TWS distribution and highlight more details as compared to smoother results from empirical post-processing filtering applied to spherical harmonics (SH) data. The prediction of vertical displacements from CSR-M and JLP-M is closer to GPS than that from SH. The residual analysis showed the reductions in WRMS (weighted root-mean-squares) from the GPS minus the CSR-M average were greater than those for JPL-M in 41 GPS stations, and the scaling factors from CLM4.0 used in JPL-M-sf had few improvements with respect to agreement with GPS measurements. Our findings indicated CSR-M solutions were more consistent with in-situ observations and more in line with actual surface mass transport in the YRB. These findings also suggested that when using GRACE mascons to detect local TWS changes or when combining GRACE-derived data with GPS-observed displacement to estimate crustal response to loadings, users should note the contributions from effects of load signal sources from atmospheric, non-tidal ocean, and difference sensitivity kernels on differences between TWS from satellite-based and in-situ observations.

Copper-Catalyzed Asymmetric Propargylation of Indolizines.

Methods to diversify indolizines are valuable for the discovery of medications and fluorescent molecules. The utilization of copper-catalyzed asymmetric propargylation to install a terminal alkyne handle on indolizine heterocycle is reported. This method delivers C3-propargylation products from C2-substituted indolizines or C1-propargylation products from C2,C3-disubstituted indolizines through a stereoconvergent pathway.

Diastereo- and Enantioselective Propargylation of 5H-Thiazol-4-ones and 5H-Oxazol-4-ones as Enabled by Cu/Zn and Cu/Ti Catalysis.

Reported is the asymmetric propargylic substitution (APS) reaction of 5H-thiazol-4-ones using a Cu/Zn dual metal catalytic system and the APS reaction of 5H-oxazol-4-ones using a Cu/Ti catalytic system. These reactions furnish functional-group-rich, terminal-alkyne-containing products with two vicinal stereocenters in high yields and with good to excellent diastereo- and enantioselectivities. This study demonstrates the use of dual metal catalytic systems as a viable approach to improve the selectivity profiles of the copper-catalyzed APS reactions.

Metal- and Base-Free Room-Temperature Amination of Organoboronic Acids with N-Alkyl Hydroxylamines.

We have found that readily available N-alkyl hydroxylamines are effective reagents for the amination of organoboronic acids in the presence of trichloroacetonitrile. This amination reaction proceeds rapidly at room temperature and in the absence of added metal or base, it tolerates a remarkable range of functional groups, and it can be used in the late-stage assembly of two complex units.

Site-Selective O-Arylation of Glycosides.

Direct and site-selective O-arylation of carbohydrates has been a challenge in synthesis. Herein we report a method based on copper-catalyzed O-arylation to address this challenge. Proper choice of the ancillary ligand on copper is critical for the efficiency and site selectivity of this transformation. This method features mild conditions, tolerates various functional groups, and demonstrates broad substrate scope.

Enantioselective Propargylation of Polyols and Desymmetrization of meso 1,2-Diols by Copper/Borinic Acid Dual Catalysis.

A copper/borinic acid dual catalytic reaction enabled the enantioselective propargylation of aliphatic polyols. Readily available reagents and catalysts were used in this transformation, which displayed good to excellent chemo- and stereoselectivity for a broad array of substrates. The method was also applicable to the desymmetrization of meso 1,2-diols to furnish products with three stereogenic centers and a terminal alkyne group in one operation.

Lobaplatin induces BGC-823 human gastric carcinoma cell apoptosis via ROS- mitochondrial apoptotic pathway and impairs cell migration and invasion.

Human gastric cancer is the fifth common cancer with considerable metastasis potential, and its high incidence and mortality rate threaten public health. In this study, we examined the anticancer effects of lobaplatin on the human gastric carcinoma cell line BGC-823 in vitro, and explored its relative mechanisms. The results of MTT assay showed dose- and time-dependent cytotoxicity in BGC-823 cells with lobaplatin. Flow cytometry (FCM) assay indicated that lobaplatin affected BGC-823 cells' survival by inducing apoptosis. Western blot analysis also demonstrated that the occurrence of its apoptosis was associated with activation of Cleaved caspase-3 and Bax, downregulation of Bcl-2. Moreover, lobaplatin could also increase the reactive oxygen species (ROS) slightly and decrease the mitochondrial membrane potential (ΔYm) obviously, elucidating that lobaplatin may induce apoptosis via mitochondria-dependent apoptotic pathway. Furthermore, lobaplatin markedly blocked BGC-823 cells migration and invasion, and the reduction of matrix metalloproteinase (MMP) MMP-2 and MMP-9 expression were also observed in vitro. Our findings demonstrated the chemotherapeutic potential of lobaplatin for treatment of human gastric carcinoma cell line BGC-823 by inhibiting proliferation, inducing apoptosis and attenuating cell migration and invasion.

Discovery and structure-activity analysis of 4-((5-nitropyrimidin-4-yl)amino)benzimidamide derivatives as novel protein arginine methyltransferase 1 (PRMT1) inhibitors.

Despite a potential application of PRMT1 inhibitors in cancer treatment, very few of PRMT1 inhibitors have been reported. To obtain novel potent PRMT1 inhibitors, structure optimizations towards a hit compound, 4-((6-chloro-5-nitropyrimidin-4-yl)amino)benzimidamide, were carried out. A series of 4-((5-nitropyrimidin-4-yl)amino)benzimidamide derivatives were synthesized. Structure-activity relationship analysis led to the discovery of a number of PRMT1 inhibitors. The most potent compound corresponds to compound 6d, which showed an IC50 value of 2.0 µM against PRMT1. This compound also displayed a considerable anti-proliferative activity against three tumor cell lines, DLD-1, T24 and SH-SY-5Y, with IC50 values of 4.4 µM, 13.1 µM and 11.4 µM, respectively.

Comparison of release and penetration of tacrolimus ointment reference and trial formulation after dermal application to pigs by liquid chromatography-electrospray ionization tandem mass spectrometry.

To investigate the consistency and bioequivalence of tacrolimus ointment reference and trial formulation, the tacrolimus concentrations in blood and skin were determined by HPLC-ESI-MS/MS following topical application of two kinds of ointment in porcine skin in a parallel, cross-over trial. The plasma protein of blood was precipitated by acetonitrile and the tacrolimus in skin was extracted by acetonitrile before HPLC-ESI-MS/MS analysis. The internal calibration method (diazepam was the internal standard) was used for quantification analysis (R(2) > 0.9999), with linear range from 0.05 to 5 ng/mL for blood samples and from 1 to 200 ng/mL for skin samples. The limits of detection for the porcine blood and skin were 0.005 and 0.5 ng/mL, respectively. The average recoveries for the porcine blood and skin spiked at three levels were 97.56-109.53 and 96.48-103.57%, respectively. The precision expressed in RSDs was from 3.43 to 10.83% for porcine blood and from 3.10 to 8.69% for porcine skin. For the same pig, the tacrolimus concentrations and variation with time of the two kinds of ointment in porcine skin were similar, although variation occurred with different individuals. These results showed that the release and penetration of tacrolimus from the reference and trial formulation are similar.

An efficient synthesis of 3-substituted indole derivates under ultrasound irradiation.

A solvent-free procedure for the synthesis of 3-substituted indole derivates from indoles and nitroalkenes under ultrasound irradiation is described. Control experiments disclosed besides mechanical effects, namely agitation, sonochemical effects are the main forces to drive the reaction. In the method, 2-chloroethanol was used to prepare a wide variety of 3-substituted indole derivates. This procedure only need equimolar amounts of reaction substrates and can be readily scaled up.

Relationship between calcium decoding elements and plant abiotic-stress resistance.

Serving as an important second messenger, calcium ion has unique properties and universal ability to transmit diverse signals that trigger primary physiological actions in cells in response to hormones, pathogens, light, gravity, and stress factors. Being a second messenger of paramount significance, calcium is required at almost all stages of plant growth and development, playing a fundamental role in regulating polar growth of cells and tissues and participating in plant adaptation to various stress factors. Many researches showed that calcium signals decoding elements are involved in ABA-induced stomatal closure and plant adaptation to drought, cold, salt and other abiotic stresses. Calcium channel proteins like AtTPC1 and TaTPC1 can regulate stomatal closure. Recently some new studies show that Ca(2+) is dissolved in water in the apoplast and transported primarily from root to shoot through the transpiration stream. The oscillating amplitudes of [Ca(2+)](o) and [Ca(2+)](i) are controlled by soil Ca(2+) concentrations and transpiration rates. Because leaf water use efficiency (WUE) is determined by stomatal closure and transpiration rate, so there may be a close relationship between Ca(2+) transporters and stomatal closure as well as WUE, which needs to be studied. The selection of varieties with better drought resistance and high WUE plays an increasing role in bio-watersaving in arid and semi-arid areas on the globe. The current paper reviews the relationship between calcium signals decoding elements and plant drought resistance as well as other abiotic stresses for further study.