Isolation, structural assignment and total synthesis of Barmumycin

Barmumycin was isolated from an extract of the marine actinomycete Streptomyces sp. BOSC-022A and found to be cytotoxic against various human tumor cell lines. Based on preliminary one- and two-dimensional 1H- and 13C-NMR spectra, the natural compound was initially assigned the structure of macrolactone-type compound 1, which was later prepared by two different routes. However, major spectroscopic differences between isolated barmumycin and 1 led to revision of the proposed structure as E-16. Based on synthesis of this new compound, and subsequent spectroscopic comparison of it to an authentic sample of barmumycin, the structure of the natural compound was indeed confirmed as that of E-16.

Macrofossils in Raraku Lake (Easter Island) integrated with sedimentary and geochemical records towards a palaeoecological synthesis for the last 34,000 years

Macrofossil analysis of a composite 19 m long sediment core from Rano Raraku Lake (Easter Island)was related to litho-sedimentary and geochemical features of the sediment. Strong stratigraphical patterns are shown by indirect gradient analyses of the data. The good correspondence between the stratigraphical patterns derived from macrofossil (Correspondence Analysis) and sedimentary and geochemical data (Principal Component Analysis) shows that macrofossil associations provide sound palaeolimnological information in conjunction with sedimentary data. The main taphonomic factors in fluencing the macrofossil assemblages are run-off from the catchment, the littoral plant belt, and the depositional environment within the basin. Five main stages during the last 34,000 calibrated years BP (cal yr BP) are characterised from the lithological, geochemical, and macrofossil data. From 34 to 14.6 cal kyr BP (last glacial period) the sediments were largely derived from the catchment, indicating a high energy lake environment with much erosion and run-off bringing abundant plant trichomes, lichens, and mosses into the centre of Raraku Lake.

Synthesis of Janus compounds for the recognition of G-U mismatched nucleobase pairs

The design and synthesis of two Janus-type heterocycles with the capacity to simultaneously recognize guanine and uracyl in G-U mismatched pairs through complementary hydrogen bond pairing is described. Both compounds were conveniently functionalized with a carboxylic function and efficiently attached to a tripeptide sequence by using solid-phase methodologies. Ligands based on the derivatization of such Janus compounds with a small aminoglycoside, neamine, and its guanidinylated analogue have been synthesized, and their interaction with Tau RNA has been investigated by using several biophysical techniques, including UV-monitored melting curves, fluorescence titration experiments, and 1H NMR. The overall results indicated that Janus-neamine/guanidinoneamine showed some preference for the +3 mutated RNA sequence associated with the development of some tauopathies, although preliminary NMR studies have not confirmed binding to G-U pairs. Moreover, a good correlation has been found between the RNA binding affinity of such Janus-containing ligands and their ability to stabilize this secondary structure upon complexation.

Rapid analysis of multiclass antibiotic residues and some of their metabolites in hospital, urban wastewater and river water by ultra-highperformance liquid chromatography coupled to quadrupole-linear ion trap tandem mass spectrometry

The present work describes the development of a fast and robust analytical method for the determination of 53 antibiotic residues, covering various chemical groups and some of their metabolites, in environmental matrices that are considered important sources of antibiotic pollution, namely hospital and urban wastewaters, as well as in river waters. The method is based on automated off-line solid phase extraction (SPE) followed by ultra-high-performance liquid chromatography coupled to quadrupole linear ion trap tandem mass spectrometry (UHPLC–QqLIT). For unequivocal identification and confirmation, and in order to fulfill EU guidelines, two selected reaction monitoring (SRM) transitions per compound are monitored (the most intense one is used for quantification and the second one for confirmation). Quantification of target antibiotics is performed by the internal standard approach, using one isotopically labeled compound for each chemical group, in order to correct matrix effects. The main advantages of the method are automation and speed-up of sample preparation, by the reduction of extraction volumes for all matrices, the fast separation of a wide spectrum of antibiotics by using ultra-high-performance liquid chromatography, its sensitivity (limits of detection in the low ng/L range) and selectivity (due to the use of tandem mass spectrometry) The inclusion of β-lactam antibiotics (penicillins and cephalosporins), which are compounds difficult to analyze in multi-residue methods due to their instability in water matrices, and some antibiotics metabolites are other important benefits of the method developed. As part of the validation procedure, the method developed was applied to the analysis of antibiotics residues in hospital, urban influent and effluent wastewaters as well as in river water samples

p-Nitrobenzyloxycarbonyl (pNZ) as Temporary Na-Protecting Group for Mild Solid-Phase Peptide Synthesis. Avoiding Diketopiperazine and Aspartimide Formation

p-Nitrobenzyloxycarbonyl was used as temporary protecting group for the -amino function in solid-phase peptide synthesis. The corresponding derivatives are solids, easy to be synthesized, and perform well in the solid-phase mode. pNZ is removed in practical neutral conditions in the presence of catalytic amounts of acid. They are orthogonal with the most common protecting groups used in peptide chemistry. They are specially useful in combination with Fmoc chemistry to overcome those side reactions associated with the used of the piperidine such DKP and aspartiimide formation. The flexibility of pNZ can be very useful for the preparation of libraries of small organic molecules.

Total synthesis of (-)-isoavenaciolide

An enantioselective approach to (-)-isoavenaciolide was achieved starting from 1- undecyn-3-ol. The synthesis relied upon the preparation of a chiral 4-silyloxy-2-alkenylborane by hydroboration of a protected 2,3-allenol and subsequent stereoselective addition to 2- thiophenecarboxaldehyde

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.

Straightforward synthesis of cyclic and bicyclic peptides

Cyclic peptide architectures can be easily synthesized from cysteine-containing peptides with appending maleimides, free or protected, through an intramolecular Michael-type reaction. After peptide assembly, the peptide can cyclize either during the trifluoroacetic acid treatment, if the maleimide is not protected, or upon deprotection of the maleimide. The combination of free and protected maleimide moieties and two orthogonally protected cysteines gives access to structurally different bicyclic peptides with isolated or fused cycles.

Vulnerability of stream biota to climate change in mediterranean climate regions: a synthesis of ecological responses and conservation challenges

Freshwater species worldwide are experiencing dramatic declines partly attributable to ongoing climate change. It is expected that the future effects of climate change could be particularly severe in mediterranean climate (med-) regions, which host many endemic species already under great stress from the high level of human development. In this article, we review the climate and climate-induced changes in streams of med-regions and the responses of stream biota, focusing on both observed and anticipated ecological responses. We also discuss current knowledge gaps and conservation challenges. Expected climate alterations have already been observed in the last decades, and include: increased annual average air temperatures; decreased annual average precipitation; hydrologic alterations; and an increase in frequency, intensity and duration of extreme events, such as floods, droughts and fires. Recent observations, which are concordant with forecasts built, show stream biota of med-regions when facing climate changes tend to be displaced towards higher elevations and upper latitudes, communities tend to change their composition and homogenize, while some life-history traits seem to provide biota with resilience and resistance to adapt to the new conditions (as being short-lived, small, and resistant to low streamflow and desiccation). Nevertheless, such responses may be insufficient to cope with current and future environmental changes. Accurate forecasts of biotic changes and possible adaptations are difficult to obtain in med-regions mainly because of the difficulty of distinguishing disturbances due to natural variability from the effects of climate change, particularly regarding hydrology. Long-term studies are needed to disentangle such variability and improve knowledge regarding the ecological responses and the detection of early warning signals to climate change. Investments should focus on taxa beyond fish and macroinvertebrates, and in covering the less studied regions of Chile and South Africa. Scientists, policy makers and water managers must be involved in the climate change dialogue because the freshwater conservation concerns are huge.