Palladium-Catalyzed α-Arylation of Carboxylic Acids and Secondary Amides via a Traceless Protecting Strategy.

A novel traceless protecting strategy is presented for the long-standing challenge of conducting the palladium-catalyzed α-arylation of carboxylic aids and secondary amides with aryl halides. Both of the presented coupling processes occur with a variety of carboxylic acids and amides and with a variety of aryl bromides containing a broad range of functional groups, including base-sensitive functionality like acyl, alkoxycarbonyl, nitro, cyano, and even hydroxyl groups. Five commercial drugs were prepared through this method in one step in 81-96% yield. Gram-scale synthesis of medication Naproxen and Flurbiprofen with low palladium loading further highlights the practical value of this method

Stereodivergent Construction of Tertiary Fluorides in Vicinal Stereogenic Pairs by Allylic Substitution with Iridium and Copper Catalysts.

Although much effort has been spent on the enantioselective synthesis of tertiary alkyl fluorides, the synthesis of compounds containing such a stereogenic center within an array of stereocenters, particularly two vicinal ones, remains a synthetic challenge, and no method to control the configuration of each stereogenic center independently has been reported. We describe a strategy to achieve such a stereodivergent synthesis of vicinal stereogenic centers, one containing a fluorine atom, by forming the connecting carbon-carbon bond with a catalyst system comprising an iridium complex that controls the configuration at the electrophilic carbon and a copper catalyst that controls the configuration at the nucleophilic fluorine-containing carbon. These reactions occur with alkyl- and aryl-substituted allylic esters and the unstabilized enolates of azaaryl ketones, esters, and amides in high yield, diastereoselectivity, and enantioselectivity (generally >90% yield, >20:1 dr, 97-99% ee). Access to all four stereoisomers of products demonstrates the precise control of the two configurations independently. This methodology extends to the stereodivergent construction of vicinal quaternary and tertiary stereocenters in similarly high yield and selectivity. DFT calculations uncover the origin of stereoselectivity of copper enolate in allylic substitution

Benzoxime carbaldehyde prevents rheumatoid arthritis in a rat model by inhibition of oxidative damage

Purpose: To investigate the effect of benzoxime carbaldehyde (BXCD) on rheumatoid arthritis (RA) in a rat model.Methods: Thirty male Sprague-Dawley rats were assigned randomly to 5 groups (6 rats per group): normal control, RA, and three treatment groups. Rats in the normal control and RA groups received normal saline, whereas those in the three treatment groups were given 2, 5 or 10 mg/kg of BXCD daily for 30 days by intraperitoneal injection. Pressure pain was analysed using electronic pressure pain detector, while the expressions of interleukin (IL)-6, interleukin (IL)-1β, nuclear factor (NF)-κB p65 and tumor necrosis factor (TNF)-α in serum were determined using enzyme-linked immunosorbent assay (ELISA) kits.Results: Treatment of RA rats with BXCD for 30 days led to significant (p < 0.05) recovery in pain threshold. At a dose of 10 mg/kg, BXCD decreased pain threshold value to a level comparable to that in normal control rats, and decreased arthritis score to 1, relative to arthritis score of 16 in untreated animals. Malondialdehyde (MDA) level was 4-fold higher in untreated RA rats than in normal and BXCD-treated groups. BXCD treatment increased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and blocked increases in the blood levels of IL-6, IL-1β, NF-κB p65 unit, and TNF-α. Western blot assay showed that BXCD treatment prevented increase in the level of cyclooxygenase-2 (COX-2) in RA rat tissues.Conclusion: These results indicate that BXCD prevents RA in a rat model via inhibition of expressions of inflammatory cytokines and decrease in oxidative stress. Thus, BXCD has a strong potential for the management of RA.Keywords: Rheumatoid arthritis, Pain threshold, Antioxidant enzymes, Inflammation, Inflammatory cytokine

Benzoxime inhibits matrix metalloproteinase-13 activation and cartilage damage in osteoarthritis rats via inhibition of NF-κB pathway

Purpose: To investigate the effect of benzoxime on degradation of  articular cartilage in a rat model of osteoarthritis (OA), and the mechanism involved.Methods: The OA rat model was prepared by injecting monosodium  iodoacetate (MIA) intra-articularly to Wistar rats. Rats in the treatment group were given benzoxime (5 mg/kg) daily for 21 days through the intra-articular route. The animals were then examined for behavioral changes by assessment of asymmetry in bearing weight and paw  withdrawal threshold of the hind limb. Western blot assay was used for the analysis of inflammatory cytokine expressions.Results: The expression of P2X purinoceptor 7 receptor (P2X7R) mRNA was significantly elevated in the OA rats (p < 0.02). However, benzoxime treatment caused a marked decrease in the level of P2X1-8R mRNA. Benzoxime treatment also prevented asymmetry in bearing weight, decreased paw withdrawal threshold, and inhibited the expressions of interleukin-1β, interleukin-6 and tumor necrosis factor-α in plasma and cartilage. Moreover, benzoxime exhibited significant inhibitory effects on the expressions of P2X7R, matrix metalloproteinase (MMP)-13 and prostaglandin E2 (PGE2) in cartilage tissue. It also significantly  suppressed OA-induced increases in the levels of inhibitor of nuclear factor-κB (NF-κB) kinase (IKK)α, IKKβ, IκBα and NF-κB p65, and blocked OA-induced increases in the expressions of P2X7R, MMP-13 and PGE2.Conclusion: These results demonstrate that benzoxime prevents cartilage degradation in OA rats by targeting NF-κB signaling pathway. Thus, benzoxime possesses clinical and therapeutic potentials for the prevention of cartilage degradation in OA.Keywords: Interleukin-1β, Purinoceptor-7, Benzoxime, Osteoarthritis, Prostaglandin, Matrix metalloproteinase

Realization of Zero-Refractive-Index Lens with Ultralow Spherical Aberration

Optical complex materials offer unprecedented opportunity to engineer fundamental band dispersion which enables novel optoelectronic functionality and devices. Exploration of photonic Dirac cone at the center of momentum space has inspired an exceptional characteristic of zero-index, which is similar to zero effective mass in fermionic Dirac systems. Such all-dielectric zero-index photonic crystals provide an in-plane mechanism such that the energy of the propagating waves can be well confined along the chip direction. A straightforward example is to achieve the anomalous focusing effect without longitudinal spherical aberration, when the size of zero-index lens is large enough. Here, we designed and fabricated a prototype of zero-refractive-index lens by comprising large-area silicon nanopillar array with plane-concave profile. Near-zero refractive index was quantitatively measured near 1.55 um through anomalous focusing effect, predictable by effective medium theory. The zero-index lens was also demonstrated to perform ultralow longitudinal spherical aberration. Such IC compatible device provides a new route to integrate all-silicon zero-index materials into optical communication, sensing, and modulation, and to study fundamental physics on the emergent fields of topological photonics and valley photonics.Comment: 14 pages, 4 figure

Application of RetCamⅡ in the screening of neonatal fundus disease

AIM: To investigate the safe and reliable examination method for neonatal fundus screening.<p>METHODS: Fundus information of 2 836 neonates performed by RetCamⅡ in our hospital from January 1, 2012 to December 31, 2012 were retrospectively analyzed, including 1 625 cases(57.30%)of premature infants which were first examined 1-4 weeks after birth and 1 211 cases(42.70%)of term infants which were first examined within 4 weeks after birth.<p>RESULTS: Totally 454 cases of abnormalfundus were found, including 207 cases(12.74%)of retinopathy of prematurity(ROP), ROPⅠ in 118 cases(57%), ROPⅡ in 58 cases(28.02%), ROPⅢ in 23 cases(11.11%), ROPⅣ in 8 cases(3.86%), no case of ROPV. A total of 247(20.40%)term infants had abnormal fundus, of which 68 cases(27.53%)were developmental or hereditary disease, retinoblastoma in 1 case(0.40%), retinal hemorrhage in 102 cases(41.30%), retinal exudative changes in 68 cases(27.53%), optic atrophy in 5 cases(2.02%)and optic disc edema in 3 cases(1.21%).<p>CONCLUSION: Neonatal fundus diseases were so various and harmful that early screening should be attended to. Premature infants and term infants with high risk are treated as focus group of fundus screening and RetCamII examination is safe and effective