Synthesis of 4-substituted-1,2-dihydroquinolines by means of gold-catalyzed intramolecular hydroarylation reaction of n-ethoxycarbonyl-n-propargylanilines

An alternative Au(I)-catalyzed synthetic route to functionalized 1,2-dihydroquinolines is reported. This novel approach is based on the use of N-ethoxycarbonyl protected-Npropargylanilines as building blocks that rapidly undergo the IMHA reaction affording the 6-endo cyclization product in good to high yields. In the presence of N-ethoxycarbonyl-N-propargyl-metasubstituted anilines, the regiodivergent cyclization at the ortho-/para-position is achieved by the means of catalyst fine tuning

Continental drift and climate change drive instability in insect assemblages

Global change has already had observable effects on ecosystems worldwide, and the accelerated rate of global change is predicted in the future. However, the impacts of global change on the stability of biodiversity have not been systematically studied in terms of both large spatial (continental drift) and temporal (from the last inter-glacial period to the next century) scales. Therefore, we analyzed the current geographical distribution pattern of Plecoptera, a thermally sensitive insect group, and evaluated its stability when coping with global change across both space and time throughout the Mediterranean region—one of the first 25 global biodiversity hotspots. Regional biodiversity of Plecoptera reflected the geography in both the historical movements of continents and the current environmental conditions in the western Mediterranean region. The similarity of Plecoptera assemblages between areas in this region indicated that the uplift of new land and continental drift were the primary determinants of the stability of regional biodiversity. Our results revealed that climate change caused the biodiversity of Plecoptera to slowly diminish in the past and will cause remarkably accelerated biodiversity loss in the future. These findings support the theory that climate change has had its greatest impact on biodiversity over a long temporal scale.This study was supported by a National Research Foundation of Korea (NRF) grant provided by the Korean government (MEST) (No. 2010-0027360)

New Species in the Old World: Europe as a Frontier in Biodiversity Exploration, a Test Bed for 21st Century Taxonomy

The number of described species on the planet is about 1.9 million, with ca. 17,000 new species described annually, mostly from the tropics. However, taxonomy is usually described as a science in crisis, lacking manpower and funding, a politically acknowledged problem known as the Taxonomic Impediment. Using data from the Fauna Europaea database and the Zoological Record, we show that contrary to general belief, developed and heavily-studied parts of the world are important reservoirs of unknown species. In Europe, new species of multicellular terrestrial and freshwater animals are being discovered and named at an unprecedented rate: since the 1950s, more than 770 new species are on average described each year from Europe, which add to the 125,000 terrestrial and freshwater multicellular species already known in this region. There is no sign of having reached a plateau that would allow for the assessment of the magnitude of European biodiversity. More remarkably, over 60% of these new species are described by non-professional taxonomists. Amateurs are recognized as an essential part of the workforce in ecology and astronomy, but the magnitude of non-professional taxonomist contributions to alpha-taxonomy has not been fully realized until now. Our results stress the importance of developing a system that better supports and guides this formidable workforce, as we seek to overcome the Taxonomic Impediment and speed up the process of describing the planetary biodiversity before it is too late

The European union’s 2010 target: Putting rare species in focus

P. 167-185The European Union has adopted the ambitious target of halting the loss of biodiversity by 2010. Several indicators have been proposed to assess progress towards the 2010 target, two of them addressing directly the issue of species decline. In Europe, the Fauna Europaea database gives an insight into the patterns of distribution of a total dataset of 130,000 terrestrial and freshwater species without taxonomic bias, and provide a unique opportunity to assess the feasibility of the 2010 target. It shows that the vast majority of European species are rare, in the sense that they have a restricted range. Considering this, the paper discusses whether the 2010 target indicators really cover the species most at risk of extinction. The analysis of a list of 62 globally extinct European taxa shows that most contemporary extinctions have affected narrow-range taxa or taxa with strict ecological requirements. Indeed, most European species listed as threatened in the IUCN Red List are narrow-range species. Conversely, there are as many wide-range species as narrow-range endemics in the list of protected species in Europe (Bird and Habitat Directives). The subset of biodiversity captured by the 2010 target indicators should be representative of the whole biodiversity in terms of patterns of distribution and abundance. Indicators should not overlook a core characteristic of biodiversity, i.e. the large number of narrow-range species and their intrinsic vulnerability. With ill-selected indicator species, the extinction of narrowrange endemics would go unnoticedS

Investigating orphan cytochromes P450 from Mycobacterium tuberculosis : the search for potential drug targets

Tuberculosis (TB) is a disease that the World Health Organisation (WHO) regards as a global pandemic. There is a great need for new drugs to combat this threat. Drug resistant strains of the causative agent, Mycobacterium tuberculosis (Mtb), have increased the urgency of this quest for novel anti-mycobacterial medicines. Publication of the Mtb genome sequence revealed a large number of cytochrome P450 (CYP) enzymes [Cole, S. T. et al. 1998]. These mono-oxygenase enzymes have been studied for many years and are responsible for metabolic functions in every kingdom of life. Research on the Mtb P450s to date has highlighted several of them as having critcal roles within the organism. CYP121 and CYP128 have been implicated as essential through gene knockout studies. It has been demonstrated that CYP125 is not essential for viability. However, it is part of a gene cluster highly important for Mtb infectivity and virulence. Due to the prospective importance of P450s to Mtb, this group of enzymes is under investigation as a source of novel drug targets. CYP142 was discovered as a potential drug target after it was located to a gene cluster involved in cholesterol catabolism during Mtb dormancy. As part of this PhD project, it was demonstrated that CYP142 performs an almost identical role to that reported for CYP125. These enzymes both perform C27 hydroxylation and carboxylation of the cholesterol side chain. However, variations in the level of oxidation have been identified, dependent upon the redox system with which these P450s are associated. A crystal structure of CYP142 showing high similarity in active site architecture to CYP125 supports the physiological role of CYP142 in cholesterol catabolism. Combining this with in vitro data which demonstrates that CYP142 possesses high affinity for a range of azole anti-fungal agents [Ahmad, Z. et al. 2005, 2006] supports the suggestion that it is a candidate target for the next generation of anti-mycobacterial drugs. CYP144 was highlighted as being important during the latent phase of Mtb growth, a phase that is not targeted by any of the current antimycobacterials. Work performed as part of this PhD has shown that many characteristics of CYP144 are highly comparable to those reported for other MtbP450s. CYP144 shows high affinity and specificity towards many azole molecules. Econazole, clotrimazole and miconazole have repeatedly been shown to bind to MtbP450s, including CYP144 and CYP142, with high affinity and are excellent potential candidates as novel anti-mycobacterial agents. An N-terminally truncated form of CYP144, CYP144-T, has been investigated in the pursuit of a CYP144 crystal structure. It is hoped that this will enable the elucidation of a physiological role for CYP144. Both CYP142 and CYP144 have demonstrated biochemical and biophysical characteristics that contribute to our knowledge of P450 enzymes. This PhD has established that CYP142 exhibits an equilibrium between P450 and P420 species in its CO-bound, ferrous form. A conversion from P420, and stabilisation of P450, upon substrate binding was also demonstrated. CYP144 displays unusual azole coordination characteristics when examined by EPR and removal of the CYP144 gene from Mtb increased sensitivity of the strain to clotrimazole. Studies of these enzymes has advanced knowledge of P450 and Mtb redox chemistry, established roles for the MtbP450 cohort and identified the potential of anti-mycobacterial drugs and associated targets.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Comparative salt tolerance of two wild Hordeum species (H.maritimum With. and H.murinum L.) from the coast of Tuscany (Italy)

The differences in salt tolerance between Hordeum maritimum and H. murinum were studied. Seeds were collected at horn maturity from wild populations growing respectively near the Orbetello Lagoon and S. Piero a Grade (Tuscany, Italy) and were used in germination and growth tests at increasing salinity (NaCl) levels. H. maritimum was confirmed to be a true halophyte as compared to H. Murinum, which exhibited germination behavior typical of many wird glycophytes. The higher salt sensitivity of H. murinum compared to H. maritimum was also shown by its shoot length values, which decreased only in H. murinum, albeit in 100 mM NaCl treatment. The higher degree of salt tolerance of H. maritimum is further demonstrated by the Na : K ratio. H. maritimum can accumulate a greater amount of sodium than potassium in both roots and shoots, even in the absence of salt treatment. However, in NaCl solutions H. maritimum showed a higher Na : K ratio for shoots - an index of better uptake and translocation of sodium to leaves - as has been for many halophyte includers. These results thus help to enhance knowledge on wild relatives of barley, whose potential contribution to genetic improvement in salinity tolerance has previously not been thoroughly explored