Total synthesis of entecavir

Entecavir (BMS-200475) was synthesized from 4-trimethylsilyl-3-butyn-2-one and acrolein. The key features of its preparation are: (i) a stereoselective boron-aldol reaction to afford the acyclic carbon skeleton of the methylenecylopentane moiety; (ii) its cyclization by a Cp2TiCl-catalyzed intramolecular radical addition of an epoxide to an alkyne; and (iii) the coupling with a purine derivative by a Mitsunobu reaction.

Peptide-decorated chitosan derivatives enhance fibroblast adhesion and proliferation in wound healing.

RGD peptide sequences are known to regulate cellular activities by interacting with α5β1, αvβ5 and αvβ3 integrin, which contributes to the wound healing process. In this study, RGDC peptide was immobilized onto chitosan derivative 1,6-diaminohexane-O-carboxymethyl-N,N,N-trimethyl chitosan (DAH-CMTMC) to display RGDC-promoting adhesion for enhanced wound healing. The efficiency of N-methylation, O-carboxymethylation and spacer grafting was quantitatively and qualitatively analyzed by (1)H NMR and FTIR, yielding 0.38 degree of substitution for N-methylation and >0.85 for O-carboxymethylation. The glass transition temperatures for chitosan derivatives were also studied. Peptide immobilization was achieved through sulfhydryl groups using sulfosuccinimidyl (4-iodoacetyl)amino-benzoate (sulfo-SIAB method). RGDC immobilized peptide onto DAH-CMTMC was found to be about 15.3μg/mg of chitosan derivative by amino acid analysis (AAA). The significant increase of human dermal fibroblast (HDF) viability in vitro over 7 days suggests that RGDC-functionalized chitosan may lead to enhanced wound healing (viability >140%). Moreover, bio-adhesion and proliferation assays confirmed that coatings of RGDC-functionalized chitosan derivatives exhibit in vitro wound healing properties by enhancing fibroblast proliferation and adhesion. These results showed that RGDC peptide-functionalized chitosan provides an optimal environment for fibroblast adhesion and proliferation.

Determination of Rod and Cone Influence to the Early and Late Dynamic of the Pupillary Light Response.

PURPOSE: This study aims to identify which aspects of the pupil light reflex are most influenced by rods and cones independently by analyzing pupil recordings from different mouse models of photoreceptor deficiency. METHODS: One-month-old wild type (WT), rodless (Rho-/-), coneless (Cnga3-/-), or photoreceptor less (Cnga3-/-; Rho-/- or Gnat1-/-) mice were subjected to brief red and blue light stimuli of increasing intensity. To describe the initial dynamic response to light, the maximal pupillary constriction amplitudes and the derivative curve of the first 3 seconds were determined. To estimate the postillumination phase, the constriction amplitude at 9.5 seconds after light termination was related to the maximal constriction amplitude. RESULTS: Rho-/- mice showed decreased constriction amplitude but more prolonged pupilloconstriction to all blue and red light stimuli compared to wild type mice. Cnga3-/- mice had constriction amplitudes similar to WT however following maximal constriction, the early and rapid dilation to low intensity blue light was decreased. To high intensity blue light, the Cnga3-/- mice demonstrated marked prolongation of the pupillary constriction. Cnga3-/-; Rho-/- mice had no pupil response to red light of low and medium intensity. CONCLUSIONS: From specific gene defective mouse models which selectively voided the rod or cone function, we determined that mouse rod photoreceptors are highly contributing to the pupil response to blue light stimuli but also to low and medium red stimuli. We also observed that cone cells mainly drive the partial rapid dilation of the initial response to low blue light stimuli. Thus photoreceptor dysfunction can be derived from chromatic pupillometry in mouse models.

Transformações químicas do (+)-10b,14-diol-allo-aromadendrano, isolado de duguetia glabriuscula r. e. fries (r. e. fries) (annonaceae) e avaliações biológicas de alguns derivados obtidos

The sesquiterpene (+)-allo-aromadendrane-10b-14-diol 1 was the lead compound to the preparation of several derivatives in order to test their biological activity against A. salina, C. sphaerospermum, E. coli and S. aureus. In this way the monoalcohols (+)-viridiflorol 4, 9 and 11 were synthesized from 1 together with the acetal 6, the ketal 7, and the ketone 8. The oxirane 3 and nitrile 5 were also prepared using as an intermediate the tosylate derivative 2.

Defeitos superficiais em 2H-WS2 observados por microscopia de tunelamento

Scanning tunnelling microscopy (STM) was used to characterise the basal surface of fresh cleaved crystals of 2H-WS2. Although no impurity or stacking faults could be detected by X-ray diffraction, STM images obtained with negative bias voltage showed two kinds of defects. These defects were attributed to an iodine derivative used as transport agent. In a flat surface free of defects, an image with atomic resolution was achieved with sulphur distances and angles as expected for hexagonal symmetry of 2H-WS2.

Identificação dos principais componentes do fungicida guazatine através da cromatografia a gás e cromatografia a gás acoplada com espectrometria de massas

Hexafluoroacetylaceton derivatives of some synthesized components of the guazatine fungicide were prepared, and their separation and identification performed through gas chromatography and gas chromatography-mass spectrometry. The chromatogram obtained from hexafluoroacetylacetone derivative of the commercial guazatine presented 14 major peaks, and 9 of them were identified through both techniques mentioned above.

Estudo de métodos de aumento de resolução de espectros de FTIR para análise de estruturas secundárias de proteínas

The FTIR spectroscopy has been used to quantify the secondary structures of proteins, using amide I band (1600 - 1700 cm-1). The resolution enhancement methods have been used to resolve the individual components of this band that correlate to the secondary structure. In this paper we discuss the methods of derivative, Fourier deconvolution and fitting with simulated spectra. The results shows that they have serious problems and can be used only as a qualitative or semiquatitative method.

Síntese e caracterização de cloro[ácido 2-(difenilfosfino)benzóico]-ouro(I) e alguns de seus derivados

In this contribution a few new gold(I)phosphine complexes, [2-(PPh2)C6H4CO 2H]AuX (where X = Cl, SCN, Br3) and a similar gold(III) derivative [{2-(PPh2)C6H4CO 2H}AuIII Cl (C6H4CH2NMe2 )]Cl have been synthesised and characterised. The phosphine, 2-(diphenylphosphino)benzoic acid, has been employed for the first time in gold chemistry. This ligand is potentially bidentate through bonding of the phosphine and carboxylate groups. The X-ray structure of the complex chloro[2-(diphenylphosphino) benzoic acid]gold(I) has been elucidated and the bond lengths encountered show great similarity to those of chloro(triphenylphosphine)gold(I). [2-(PPh2)C6H4CO 2H]AuCl crystallises in the space group P2(1)/c with a = 9.113(2) Å, b = 10.925(2) Å, c = 23.069(4) Å, beta = 99.95º(3), V = 2299 ų, Z = 4 and R = 0.091. Biological tests for anti-fungal and anti-bacterial activity demostrate that [2-(PPh2)C6H4CO 2H]AuCl exhibits broad spectrum activity against a range of organisms.

Novos derivados do sistema heterocíclico 1H-pirazolo[3,4-b]piridina: síntese e assinalamentos de hidrogênios e carbonos por RMN 1D e 2D

The synthesis and NMR analysis of seven new 4-(aryl)amino-5-carboethoxy-1,3-dimethyl-1H-pyrazolo[3,4- b]pyridines (7-13) are described. The synthetic approach used involved the preparation of intermediates 5-aminopyrazol (4), the enamine derivative (5) and the 4-chloro-1H-pyrazolo[3,4-b]pyridine (6). Compounds (7-13) were obtained by treatment of 6 with the desired aniline. The structures of new heterocyclic compounds and their precursors intermediates were assigned on the basis of spectral analysis including 1D and 2D NMR experiments [¹H; 13C{¹H} and DEPT; ¹H x ¹H - COSY; ¹H x13C - COSY, nJ CH, n = 1, 2 or 3 (HETECOR and COLOC)].

Spectrophotometric determination of cefaclor in pharmaceutical preparations

A simple spectrophotometric method is proposed for the determination of cefaclor. The method involves alkaline hydrolysis of the drug in ammonia buffer solution at pH 10 to yield diketopiperazine-2,5-dione derivative and subsequent measurement at 340 nm. Beer's law is obeyed in the concentration range 1.8 - 55 mg/mL. The proposed method was successfully applied to the determination of cefaclor in pharmaceutical formulations.

Reduction and Analysis Methods of Indigo

Throughout history indigo was derived from various plants for example Dyer’s Woad (Isatis tinctoria L.) in Europe. In the 19th century were the synthetic dyes developed and nowadays indigo is mainly synthesized from by-products of fossil fuels. Indigo is a so-called vat dye, which means that it needs to be reduced to its water soluble leucoform before dyeing. Nowadays, most of the industrial reduction is performed chemically by sodium dithionite. However, this is considered environmentally unfavourable because of waste waters contaminating degradation products. Therefore there has been interest to find new possibilities to reduce indigo. Possible alternatives for the application of dithionite as the reducing agent are biologically induced reduction and electrochemical reduction. Glucose and other reducing sugars have recently been suggested as possible environmentally friendly alternatives as reducing agents for sulphur dyes and there have also been interest in using glucose to reduce indigo. In spite of the development of several types of processes, very little is known about the mechanism and kinetics associated with the reduction of indigo. This study aims at investigating the reduction and electrochemical analysis methods of indigo and give insight on the reduction mechanism of indigo. Anthraquinone as well as it’s derivative 1,8-dihydroxyanthraquinone were discovered to act as catalysts for the glucose induced reduction of indigo. Anthraquinone introduces a strong catalytic effect which is explained by invoking a molecular “wedge effect” during co-intercalation of Na+ and anthraquinone into the layered indigo crystal. The study includes also research on the extraction of plant-derived indigo from woad and the examination of the effect of this method to the yield and purity of indigo. The purity has been conventionally studied spectrophotometrically and a new hydrodynamic electrode system is introduced in this study. A vibrating probe is used in following electrochemically the leuco-indigo formation with glucose as a reducing agent.

Constituintes químicos das raízes de Pyrostegia Venusta e considerações sobre a sua importância medicinal

This paper describes the chemical constituents isolated from roots of Pyrostegia venusta. From ethanol extract of the roots allantoin, beta-sitosterol, 3b-O-beta-D-glupyranosylsitosterol and hesperedin were isolated. The structures of these natural products were identified on the basis of spectral data, including 2D NMR of the peracetyl derivative of hesperidin.

An update on EMU sovereign yield spread drivers in times of crisis: A panel data analysis

We empirically investigate the determinants of EMU sovereign bond yield spreads with respect to the German bund. Using panel data techniques, we examine the role of a wide set of potential drivers. To our knowledge, this paper presents one of the most exhaustive compilations of the variables used in the literature to study the behaviour of sovereign yield spreads and, in particular, to gauge the effect on these spreads of changes in market sentiment and risk aversion. We use a sample of both central and peripheral countries from January 1999 to December 2012 and assess whether there were significant changes after the outbreak of the euro area debt crisis. Our results suggest that the rise in sovereign risk in central countries can only be partially explained by the evolution of local macroeconomic variables in those countries.

An update on EMU sovereign yield spread drivers in times of crisis: A panel data analysis

We empirically investigate the determinants of EMU sovereign bond yield spreads with respect to the German bund. Using panel data techniques, we examine the role of a wide set of potential drivers. To our knowledge, this paper presents one of the most exhaustive compilations of the variables used in the literature to study the behaviour of sovereign yield spreads and, in particular, to gauge the effect on these spreads of changes in market sentiment and risk aversion. We use a sample of both central and peripheral countries from January 1999 to December 2012 and assess whether there were significant changes after the outbreak of the euro area debt crisis. Our results suggest that the rise in sovereign risk in central countries can only be partially explained by the evolution of local macroeconomic variables in those countries.

Inhibition of nociceptive responses after systemic administration of amidated kyotorphin

BACKGROUND AND PURPOSE Kyotorphin (KTP; L-Tyr-L-Arg), an endogenous neuropeptide, is potently analgesic when delivered directly to the central nervous system. Its weak analgesic effects after systemic administration have been explained by inability to cross the blood-brain barrier (BBB) and detract from the possible clinical use of KTP as an analgesic. In this study, we aimed to increase the lipophilicity of KTP by amidation and to evaluate the analgesic efficacy of a new KTP derivative (KTP-amide - KTP-NH 2). EXPERIMENTAL APPROACH We synthesized KTP-NH 2. This peptide was given systemically to assess its ability to cross the BBB. A wide range of pain models, including acute, sustained and chronic inflammatory and neuropathic pain, were used to characterize analgesic efficacies of KTP-NH 2. Binding to opioid receptors and toxicity were also measured. KEY RESULTS KTP-NH 2, unlike its precursor KTP, was lipophilic and highly analgesic following systemic administration in several acute and chronic pain models, without inducing toxic effects or affecting motor responses and blood pressure. Binding to opioid receptors was minimal. KTP-NH 2 inhibited nociceptive responses of spinal neurons. Its analgesic effects were prevented by intrathecal or i.p. administration of naloxone. CONCLUSIONS AND IMPLICATIONS Amidation allowed KTP to show good analgesic ability after systemic delivery in acute and chronic pain models. The indirect opioid-mediated actions of KTP-NH 2 may explain why this compound retained its analgesic effects although the usual side effects of opioids were absent, which is a desired feature in next-generation pain medications