Axially disymmetric tertiary amines or quaternary ammonium salts are synthesized by double alkylation of primary or secondary amines with racemic or optically pure 2,2′-bis (bromomethyl)-1,1′-binaphthyl. Their reductive cleavage by lithium aluminium hydride in refluxing THF leads to chiral secondary or tertiary amines , substituted by a binaphthyl unit, with high yields and absence of racemization. 相似文献
The bicyclic monoselenoacetal 7 , easily obtained from (±)-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 6 ) via a radical addition-acyl migration sequence, was converted to racemic 12-epiprostaglandins 3 and 4 . The key intermediate was the all-cis-formyllactone 2b related to Corey lactone (see 12 ; Scheme 1). The presence of a (tert-butyl)-dimethylsilyl protective group for the 11-OH substituent (prostaglandin numbering) was found to be crucial in avoidingβ -elimination and epimerization during the Wittig-Horner reaction (Scheme 2). Epimerization at C(12) at the formyllactone stage (see 2b ) was also possible and gave the known precursor 1b of naturally occurring prostaglandins and analogs. 相似文献
The study and extension of a simple automated clean-up method for polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) to a broad range of polychlorinated biphenyls (PCB) is described. The isolation of seven PCDD, ten PCDF, and three coplanar PCB (cPCB) is extended to eight monoortho substituted PCB and seven so-called "marker PCB" (Aroclor 1260) for fatty food samples. This enables quantification of 35 compounds - including all congeners with a WHO toxic equivalent factor (TEF)--in a single extraction and single purification step. The chromatographic behaviour of mono-ortho PCB and marker PCB on a variety of adsorbents, including basic alumina, has been studied. Partitioning of analytes through multi-column sequences is described and correlated with their structural and electronic properties, by use of molecular modelling calculations. The fractionation process available with the Power-Prep automated clean-up system enables rapid independent analysis of the different groups of compounds. Gas chromatography with high resolution mass spectrometry (GC-HRMS) is used for the PCDD/F and cPCB fraction and quadrupole ion-storage tandem in time mass spectrometry (GC-QISTMS) for analysis of the remaining PCB. A comparison study was performed on quality-control samples and real fatty food samples to evaluate the robustness of the new strategy compared with a reference method. On the basis of this simultaneous clean-up, a rapid simplified strategy for PCDD/F and selected PCB analysis determination is proposed for fatty food samples. 相似文献
[reaction: see text]. A procedure for the chemical synthesis of [3-15N]-labeled pseudouridine and a methylated derivative was developed. A suitably protected pseudouridine precursor was nitrated at N3 followed by treatment with 15NH4Cl to afford the 15N-labeled product in six steps with a 20% yield. This methodology will allow for the production of RNAs with [3-15N]pseudouridine and [3-15N-methyl]pseudouridine at specific locations. 相似文献
Recent developments in trapping efficiency inside ion trap mass spectrometer permitted to lower instrument detection limit (IDL). An IDL of 200 fg μl−1 injected with a signal-to-noise ratio of 5:1 for tetrachlorodibenzo-p-dioxin (TCDD) was obtained by gas chromatography coupled to a quadrupole ion storage mass spectrometer in tandem mode (GC/MS/MS). Coupling large volume programmable temperature vaporizer (PTV-LV) injection to GC/MS/MS provides an alternative and complementary method to classical splitless-GC injection connected to high-resolution mass spectrometry (splitless-GC/HRMS) method for dioxin monitoring in food and feed.
An injection volume of 10 μl was found to be the best compromise between the sensitivity requirements and the robustness required for a high throughput method. PTV-LV-GC/MS/MS and Splitless-GC/HRMS were compared by performing analysis on five different matrices such as beef fat, yolk eggs, milk powder, animal feed and serum samples covering a concentration range of two orders of magnitude (i.e. 0.2–25 ng WHO-TEQ kg−1). An analysis of variance (ANOVA) was carried out. Fisher tests pointed out that the method effect for all the 2,3,7,8 congeners was not significant, indicating that the null hypothesis (H0: μ1=μ2=…=μn) was not rejected. Moreover, the interaction effects between methods and matrices were not significant for most of the 2,3,7,8 congeners. However, three congeners (2,3,7,8-TCDF; 1,2,3,4,7,8-HxCDD and 1,2,3,4,6,7,8-HpCDD) were characterized by P-values lower than the significance level (=0.05). In toxic equivalence (TEQ), the study showed that no significant bias was observed between the two methods. Consequently, PTV-LV-GC/MS/MS is an attractive technique and can be used as a cost effective complementary method to HRMS for dioxin levels monitoring in food and feed. 相似文献
Carbon nanotubes (CNTs) constitute a class of nanomaterials that possess characteristics suitable for a variety of possible applications. Their compatibility with aqueous environments has been made possible by the chemical functionalization of their surface, allowing for exploration of their interactions with biological components including mammalian cells. Functionalized CNTs (f-CNTs) are being intensively explored in advanced biotechnological applications ranging from molecular biosensors to cellular growth substrates. We have been exploring the potential of f-CNTs as delivery vehicles of biologically active molecules in view of possible biomedical applications, including vaccination and gene delivery. Recently we reported the capability of ammonium-functionalized single-walled CNTs to penetrate human and murine cells and facilitate the delivery of plasmid DNA leading to expression of marker genes. To optimize f-CNTs as gene delivery vehicles, it is essential to characterize their interactions with DNA. In the present report, we study the interactions of three types of f-CNTs, ammonium-functionalized single-walled and multiwalled carbon nanotubes (SWNT-NH3+; MWNT-NH3+), and lysine-functionalized single-walled carbon nanotubes (SWNT-Lys-NH3+), with plasmid DNA. Nanotube-DNA complexes were analyzed by scanning electron microscopy, surface plasmon resonance, PicoGreen dye exclusion, and agarose gel shift assay. The results indicate that all three types of cationic carbon nanotubes are able to condense DNA to varying degrees, indicating that both nanotube surface area and charge density are critical parameters that determine the interaction and electrostatic complex formation between f-CNTs with DNA. All three different f-CNT types in this study exhibited upregulation of marker gene expression over naked DNA using a mammalian (human) cell line. Differences in the levels of gene expression were correlated with the structural and biophysical data obtained for the f-CNT:DNA complexes to suggest that large surface area leading to very efficient DNA condensation is not necessary for effective gene transfer. However, it will require further investigation to determine whether the degree of binding and tight association between DNA and nanotubes is a desirable trait to increase gene expression efficiency in vitro or in vivo. This study constitutes the first thorough investigation into the physicochemical interactions between cationic functionalized carbon nanotubes and DNA toward construction of carbon nanotube-based gene transfer vector systems. 相似文献
The synthesis of 3-methylpseudouridine (m(3)Psi) phosphoramidite, 5'-O-[benzhydryloxybis(trimethylsilyloxy)silyl]-2'-O-[bis(2-acetoxyethoxy)methyl]-3-methylpseudouridine-3'-(methyl-N,N-diisopropyl)phosphoramidite, is reported. Selective pivaloyloxymethyl protection of the Psi N1 followed by methylation at N3 was used to generate the naturally occurring pseudouridine analogue. The m(3)Psi phosphoramidite was used in combination with pseudouridine (Psi) and standard base phosphoramidites to synthesize a 19-nucleotide RNA representing helix 69 of Escherichia coli 23S ribosomal RNA (rRNA) (residues 1906-1924), containing a single m(3)Psi at position 1915 and two Psi's at positions 1911 and 1917. Our synthesis of the fully modified helix 69 RNA demonstrates the ability to make milligram quantities of RNA that can be used for further high-resolution structure studies. Site-selective introduction of the methyl group at the N3 position of pseudouridine at position 1915 causes a slight increase in the thermodynamic stability of the RNA hairpin relative to pseudouridine; RNAs containing either uridine or 3-methyluridine at position 1915 have similar stability. One-dimensional imino proton NMR and circular dichroism spectra of the modified RNAs reveal that the methyl group does not cause any substantial changes in the RNA hairpin structure. 相似文献
Treatment of 2,2'-bis(bromomethyl)-1,1'-binaphthyl [(R,S)-2] with 1,1'-binaphthalene-2,2'-diol (+)-(R)-1 and cesium or potassium carbonate in refluxing acetone, gave the diastereoisomeric dioxacyclophanes (-)-(R,S)-3a and (+)-(R,R)-3b, both obtained in high yield, and the cyclic tetraether (+)-(R,R,R,S)-4 as isolated side product. Boron tribomide-promoted ether cleavage of 3a and 3b gave optically pure (-)-(S)-2 and (+)-(R)-2, respectively, and the recovered diol (+)-(R)-1. Alternatively, the same reaction sequence furnished the resolved diols (-)-(S)-1 and (+)-(R)-1 from (R,S)-1 and (+)-(R)-2, as well as optically pure 2,2'-bis(chloromethyl)-1,1'-binaphthyl (+)-(R)-5 from the racemic dibromide (R,S)-2 by using boron trichloride for ether cleavage. 相似文献
Inhibitors for matrix metalloproteinases (MMPs) are under investigation for the treatment of cancer, arthritis, and cardiovascular disease. Here, we report a class of highly selective MMP-13 inhibitors (pyrimidine dicarboxamides) that exhibit no detectable activity against other MMPs. The high-resolution X-ray structures of three molecules of this series bound to MMP-13 reveal a novel binding mode characterized by the absence of interactions between the inhibitors and the catalytic zinc. The inhibitors bind in the S1' pocket and extend into an additional S1' side pocket, which is unique to MMP-13. We analyze the determinants for selectivity and describe the rational design of improved compounds with low nanomolar affinity. 相似文献
An extended family of heterometallic [(M1)2(M2)2(L-)4](n+) [2x2] grid-type arrays 1-9 has been prepared. The three-tiered synthetic route encompasses regioselective, redox and enantioselective features and is based on the stepwise construction of heteroditopic hydrazone ligands A-C. These ligands contain ionisable NH and nonionisable NMe hydrazone units, which allows the metal redox properties to be controlled according to the charge on the ligand binding pocket. The 2-pyrimidine (R) and 6-pyridine (R') substituents have a significant effect on complex geometry and influence both the electrochemical and magnetic behaviour of the system. 1H NMR spectroscopic studies show that the Fe(II) ions in the grid can be low spin, high spin or spin crossover depending on the steric effect of substituents R and R'. This steric effect has been manipulated to construct an unusual array possessing two low-spin and two spin-crossover Fe(II) centres (grid 8). Electrochemical studies were performed for the grid-type arrays 1-9 and their respective mononuclear precursor complexes 10-13. The grids function as electron reservoirs and display up to eight monoelectronic, reversible reduction steps. These processes generally occur in pairs and are assigned to ligand-based reductions and to the Co(III)/Co(II) redox couple. Individual metal ions in the heterometallic grid motif can be selectively addressed electrochemically (e.g., either the Co(III) or Fe(II) ions can be targeted in grids 2 and 5). The Fe(II) oxidation potential is governed by the charge on the ligand binding unit, rather than the spin state, thus permitting facile electrochemical discrimination between the two types of Fe(II) centre in 7 or in 8. Such multistable heterometallic [2x2] gridlike arrays are of great interest for future supramolecular devices incorporating multilevel redox activity. 相似文献