Flexible synthesis of enantiomerically pure 2,8-dialkyl-1,7-dioxaspiro[5.5]undecanes and 2,7-dialkyl-1,6-dioxaspiro[4.5]decanes from propargylic and homopropargylic alcohols

A new approach to enantiomerically pure 2,8-dialkyl-1,7-dioxaspiro[5.5]undecanes and 2,7-dialkyl-1,6-dioxaspiro [4.5] decanes is described and utilizes enantiomerically pure homopropargylic alcohols obtained from lithium acetylide opening of enantiomerically pure epoxides, which are, in turn, acquired by hydrolytic kinetic resolution of the corresponding racemic epoxides. Alkyne carboxylation and conversion to the Weinreb amide may be followed by triple-bond manipulation prior to reaction with a second alkynyllithium derived from a homo- or propargylic alcohol. In this way, the two ring components of the spiroacetal are individually constructed, with deprotection and cyclization affording the spiroacetal. The procedure is illustrated by acquisition of (2S,5R,7S) and (2R,5R,7S)-2-n-butyl-7-methyl-1,6-dioxaspiro[4.5]-decanes (1), (2S,6R,8S)-2-methyl-8-n-pentyl-1,7-dioxaspiro[5.5]undecane (2), and (2S,6R,8S)-2-methyl-8-n-propyl-1,7-dioxaspiro[5.5]undecane (3). The widely distributed insect component, (2S,6R,8S)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane (4), was acquired by linking two identical alkyne precursors via ethyl formate. In addition, [H-2(4)]-regioisomers, 10,10,11,11-[H-2(4)] and 4,4,5,5-[H-2(4)] of 3 and 4,4,5,5-[H-2(4)]-4, were acquired by triple-bond deuteration, using deuterium gas and Wilkinson's catalyst. This alkyne-based approach is, in principle, applicable to more complex spiroacetal systems not only by use of more elaborate alkynes but also by triple-bond functionalization during the general sequence.

Simultaneous determination of morphine, oxycodone, morphine-3-glucuronide, and noroxycodone concentrations in rat serum by high performance liquid chromatography-electrospray ionization-tandem mass spectrometry

An assay using high performance liquid chromatography (HPLC)-electrospray ionization-tandem mass spectrometry (ESI-MS-MS) was developed for simultaneously determining concentrations of morphine, oxycodone, morphine-3-glucuronide, and noroxycodone, in 50 mul samples of rat serum. Deuterated (d(3)) analogues of each compound were used as internal standards. Samples were treated with acetonitrile to precipitate plasma proteins: acetonitrile was removed from the supernatant by centrifugal evaporation before analysis. Limits of quantitation (ng/ml) and their between-day accuracy and precision (%deviation and %CV) were-morphine, 3.8 (4.3% and 7.6%); morphine-3-glucuronide, 5.0 (4.5% and 2.9%); oxycodone, 4.5 (0.4% and 9.3%); noroxycodone, 5.0 (8.5% and 4.6%). (C) 2004 Elsevier B.V. All rights reserved.

Novel anti-bacterials against MRSA:Synthesis of focussed combinatorial libraries of tri-substituted 2(5H)-furanones

Mucobromic and mucochloric acid were used as building blocks for the construction of a chemical combinatorial library of 3,4,5-trisubstituted 2(5H)-furanones. With these 2 butenolide building blocks, and eight alcohols a sublibrary of 16 dihalogenated 5-alkoxy-2(5H)-furanones was prepared. This sublibrary of 5-alkoxylated furanones was reacted with 16 amines generating a full size focussed combinatorial library of 256 individual compounds. This three dimensional combinatorial library of 3-halogen-4-amino-5-alkoxy-2(5H)-furanones was prepared around the benzimidazolyl furanone lead structure by applying a solution phase combinatorial chemistry concept. Typical representatives of the library were purified and fully characterized and one x-ray structures was recorded, additionally. The 3-bromo-4-benzimizazolyl-5-methoxy-2(5H)furanone, Br-A-l, showed an MIC of 8 μg/ml against the multiresistant Staphylococcus aureus ( MRSA). © 2006 Bentham Science Publishers Ltd.

CuII chain compound showing a ferromagnetic coupling through triple N1,N2-1,2,4-triazole bridges

[Cu(hyetrz)3](CF3SO3)2·H2O [hyetrz = 4-(2′-hydroxyethyl)-1,2,4-triazole] represents the first structurally characterised ferromagnetically coupled CuII chain compound containing triple N1,N2-1,2,4-triazole bridges. catena-[μ-Tris{4-(2′-hydroxyethyl)-1,2,4-triazole-N1,N2}copper(II)] bis(trifluoromethanesulfonate) hydrate (C14H23F6S2O10CuN9) crystallises in the triclinic space group Pl, a = 13.54(3), b = 14.37(3), c = 15.61(4) Å, α = 95.9(1), β = 104.9(1), γ = 106.5(1)°, V = 2763(11) Å3, Z = 4 (CuII units). The CuII ions are linked by triple N1,N2-1,2,4-triazole bridges yielding an alternating chain with Cu1−Cu2 = 3.8842(4) Å and Cu2−Cu3 = 3.9354(4) Å. Analysis of the magnetic data according to a high-temperature series expansion gives a J value of +1.45(3) cm−1. The nature and the magnitude of the ferromagnetic exchange have been discussed on the basis of the structural features. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).

Structural determinants of oligomerization of the aquaporin-4 channel

The aquaporins (AQP) family of integral membrane protein channels mediate cellular water and solute flow. Although qualitative and quantitative differences in channel permeability, selectivity, subcellular localization and trafficking responses have been observed for different members of the AQP family, the signature homotetrameric quaternary structure is conserved. Using a variety of biophysical techniques, we show that mutations to an intracellular loop (loop D) of human AQP4 reduce oligomerization. Non-tetrameric AQP4 mutants are unable to relocalize to the plasma membrane in response to changes in extracellular tonicity, despite equivalent constitutive surface expression levels and water permeability to wild-type AQP4. A network of AQP4 loop D hydrogen bonding interactions, identified using molecular dynamics simulations and based on a comparative mutagenic analysis of AQPs 1, 3 and 4, suggest that loop D interactions may provide a general structural framework for tetrameric assembly within the AQP family.

Conformational analysis of the natural iron chelator myo-inositol 1,2,3-trisphosphate using a pyrene-based fluorescent mimic

myo-Inositol phosphates possessing the 1,2,3-trisphosphate motif share the remarkable ability to completely inhibit iron-catalysed hydroxyl radical formation. The simplest derivative, myo-inositol 1,2,3-trisphosphate [Ins(1,2,3)P3], has been proposed as an intracellular iron chelator involved in iron transport. The binding conformation of Ins(1,2,3)P3 is considered to be important to complex Fe3+ in a 'safe' manner. Here, a pyrene-based fluorescent probe, 4,6-bispyrenoyl-myo-inositol 1,2,3,5-tetrakisphosphate [4,6-bispyrenoyl Ins(1,2,3,5)P4], has been synthesised and used to monitor the conformation of the 1,2,3-trisphosphate motif using excimer fluorescence emission. Ring-flip of the cyclohexane chair to the penta-axial conformation occurs upon association with Fe3+, evident from excimer fluorescence induced by π-π stacking of the pyrene reporter groups, accompanied by excimer formation by excitation at 351 nm. This effect is unique amongst biologically relevant metal cations, except for Ca 2+ cations exceeding a 1:1 molar ratio. In addition, the thermodynamic constants for the interaction of the fluorescent probe with Fe3+ have been determined. The complexes formed between Fe 3+ and 4,6-bispyrenoyl Ins(1,2,3,5)P4 display similar stability to those formed with Ins(1,2,3)P3, indicating that the fluorescent probe acts as a good model for the 1,2,3-trisphosphate motif. This is further supported by the antioxidant properties of 4,6-bispyrenoyl Ins(1,2,3,5)P4, which closely resemble those obtained for Ins(1,2,3)P3. The data presented confirms that Fe3+ binds tightly to the unstable penta-axial conformation of myo-inositol phosphates possessing the 1,2,3-trisphosphate motif. © 2010 The Royal Society of Chemistry.

Fragm. lat. II 4 - Elenchi sophistici, mit Rand- und Interlinearglossen

Trägerbände: Inc. oct. 464 Bd. 2; Inc. oct. 464 Bd. 4; Ms. Praed. 153; ein Band mit unbekannter Signatur; Vorbesitzer: Dominikanerkloster Frankfurt am Main

Isotopes content, mineralogical composition, Uranium and Thorium contents and determined activity ratios from METEOR cruise M74/3 in 2007

Authigenic carbonate deposits have been sampled with the remotely operated vehicle 'MARUM-QUEST 4000 m' from five methane seeps between 731 and 1823 m water depth along the convergent Makran continental margin, offshore Pakistan (northern Arabian Sea). Two seeps on the upper slope are located within the oxygen minimum zone (OMZ; ca. 100 to 1100 m water depth), the other sites are situated in oxygenated water below the OMZ (below 1100 m water depth). The carbonate deposits vary with regard to their spatial extent, sedimentary fabrics, and associated seep fauna: Within the OMZ, carbonates are spatially restricted and associated with microbial mats, whereas in the oxygenated zone below the OMZ extensive carbonate crusts are exposed on the seafloor with abundant metazoans (bathymodiolin mussels, tube worms, galatheid crabs). Aragonite and Mg-calcite are the dominant carbonate minerals, forming common early diagenetic microcrystalline cement and clotted to radial-fibrous cement. The delta18O carbonate values range from 1.3 to 4.2 per mil V-PDB, indicating carbonate precipitation at ambient bottom-water temperature in shallow sediment depth. Extremely low delta13Ccarbonate values (as low - 54.6per mil V-PDB) point to anaerobic oxidation of methane (AOM) as trigger for carbonate precipitation, with biogenic methane as dominant carbon source. Prevalence of biogenic methane in the seepage gas is corroborated by delta13C methane values ranging from - 70.3 to - 66.7per mil V-PDB, and also by back-calculations considering delta 13C methane values of carbonate and incorporated lipid biomarkers.

Granulometry of surface sediments from the Panama Basin (Table 2, 3)

Panama Basin sediment surface coarse fractions are dominantly composed of planktonic foraminiferal remains. Textural studies of these coarse fractions by means of a large diameter settling tube system reveal characteristics grain size spectra with important modes at 2.0-2.25 phi, 2.3-2.45 phi, 2.5-2.75 phi, 3.0-33 phi, and 3.4-3.75 phi. The coarser modes consist of large Globoquadrina dutertrei and Globorotalia menardii shells, the finer ones of small planktonic foraminiferal species and of shell fragments of the larger species. Analyses of samples from the Carnegie Gap provide sufficient information such that the extent of the high energy environment close to the sill depth can be mapped; the textural analyses also seem to indicate south and northward flowing components of the bottom currents which transport particle assemblages with distinct textural characteristics. The samples bear evidence for large scale removal of calcareous fines from the crest of structural highs; the fines are then dumped on the flanks of these elevations.

Descriptions of 104 gravity and piston sediment cores from POLARSTERN expedition ARK-VIII/3 to the Arctic Ocean

Sediment descriptions and lithostratigraphy (chapter 6.4) NANSEN BASIN The upperrnost 20-50 cm of sedirnents in the Nansen Basin norrnally cornprise soft dark brown, brown-grayish and brown clay. Except for the toprnost clay, the four piston cores retrieved, contained quite different lithologies: a rnuddy diarnicton with outsized clasts (PS2157-6), sandy-silt beds alternating with clay beds (PS2159-6), and silty clay beds of brownish and grayish colours (PS2161-3). Core PS2208-3 was retrieved frorn a plateau on a searnount. The plateau was serni-encircled by hills. The upper 250 cm of this core cornprise brown and olive brown clays. Below these are several sandlayers and a 74 cm thick unit of a sandy mud with rnud-clasts up to 20 cm in diameter. GAKKEL RIDGE The uppermost 20-50 cm of sediments on the Gakkel Ridge comprise soft dark brown, brown, grayish brown clay. In most of the cores there are two horizons of brown clay separated by olive brown clay. The upper horizon is darker. The older stratigraphy is rather varied. Core PS2165-1 contains several thin gray sandlsilt layers, probably distal turbidites. The sarne is found in Core PS2167-1. This core also has a thick (approx. 2 rn) coarse grained turbidite containing large rnud clasts and basaltic rock fragrnents. The color of the turbiditic layers is dark gray. There are several horizons of hernipelagic sandylsilty clays with quite a variety in colours; black, gray, olive, brown, yellowish brown and reddish. The colour variation rnay be due to hydrotherrnal activity or provenance or a shift in redox potential. Cores PS2168-2 and PS2169-1 have typical sequences of very dark gray sandy mud with sharp lower boundaries grading upwards into olive brown clay. Below the lower boundary is often a thin (1-2 cm) gray clay layer. AMUNDSEN BASIN The giant box cores (GKG) provided in most cases excellently preserved sedirnent surfaces which consisted in the entire Amundsen Basin of dark brown to dark grayish brown silty clay with few dropstones and common calcareous microfossils (foraminifers and calcareous nannofossils). The brown and grayish brown color of the sediment surface is a result of the oxidizing conditions at the seafloor due to the rapid renewal of the bottom water rnasses. Planktic forarninifers and calcareous nannofossils are relatively frequent and well preserved despite the rernote location of the basin and its water depths of >4000 rn. Srnear slide descriptions have shown that the surface sedirnents consist dorninantly of clays to silty rnuds with clay rninerals and quartz as the rnost important constituents. The coarse fractions contained besides planktic and benthic forarninifers and coarse clastic rnaterials, rare bivalves, dropstones and mud clasts. The Station PS2190 at the North Pole is a particular good exarnple of the type of sedirnents deposited at the sea floor surface of the Arnundsen Basin, with hornogenous dark brown soft clay covering a sedirnent sequence of highly variable cornposition. Nurnerous giant box cores also provide insight into the detailed lithostratigraphy of the upperrnost sedirnent layers. Twelve box cores have been collected frorn the Arnundsen Basin. Below the youngest unit of 5-20 crn thick silty clays deposits of variable stratigraphies have been found, rnostly consisting of clays or silty clays. In a few instances turbidites have been observed. Benthic forarninifers have not been found in the surface sedirnents. Other fossils were extrernely rare. Bioturbation is weakly developed on all stations. Benthic anirnals seern to live only in and on the upperrnost 2 cm of the uppermost sediment layer. They cornprise amphipods (on all stations) and holothurians, bryozoans, polychaetes, and porifers at one station each. LOMONOSOV RIDGE Sediments from the Lomonosov Ridge show a variety of colors and textures. Following smear slide analyses they are composed mostly of clay minerals and quartz with mica and feldspars, especially in the siltier and sandier parts. Volcanic glass, microcrystalline carbonate, opaque minerals and green amphibole are occasional accessories. The sediments from the Lomonosov Ridge show a noticeable difference from sediments collected from the surrounding basins. Lomonosov Ridge sediments are richer in silt and sand than basin sediments. Occasional turbidites occur in ridge sediments but these must be of entirely local origin. The ridge sediments include frequent layers of "cottage cheese" texture made up of what appear to be small, angular mud clasts of a variety of colors.

Biomarker distributions in sediment core PS2767-4

Here, we present a first (low-resolution) biomarker sea-ice proxy record from the High Arctic (southern Lomonosov Ridge), going back in time to about 60 ka (MIS 3 to MIS 1). Variable concentrations of the sea-ice diatom specific highly branched isoprenoid (HBI) with 25 carbon atoms ("IP25"), in combination with the phytoplankton biomarker brassicasterol, suggest variable seasonal sea-ice coverage and open-water productivity during MIS 3. During most of MIS 2, the spring to summer sea-ice margin significantly extended towards the south, resulting in a drastic decrease in phytoplankton productivity. During the Early Holocene Climate Optimum, brassicasterol reached its maximum, interpreted as signal for elevated phytoplankton productivity due to a significantly reduced sea-ice cover. During the mid-late Holocene, IP25 increased and brassicasterol decreased, indicating extended sea-ice cover and reduced phytoplankton productivity, respectively. The HBI diene/IP25 ratios probably reached maximum values during the Bølling-Allerød warm period and decreased during the Holocene, suggesting a correlation with sea-surface temperature.