Kinetically E-selective macrocyclic ring-closing metathesis

Macrocyclic compounds are central to the development of new drugs, but preparing them can be challenging because of the energy barrier that must be surmounted in order to bring together and fuse the two ends of an acyclic precursor such as an alkene (also known as an olefin). To this end, the catalytic process known as ring-closing metathesis (RCM) has allowed access to countless biologically active macrocyclic organic molecules, even for large-scale production. Stereoselectivity is often critical in such cases: The potency of a macrocyclic compound can depend on the stereochemistry of its alkene; alternatively, one isomer of the compound can be subjected to stereoselective modification (such as dihydroxylation). Kinetically controlled Z-selective RCM reactions have been reported, but the only available metathesis approach for accessing macrocyclic E-olefins entails selective removal of the Z-component of a stereoisomeric mixture by ethenolysis, sacrificing substantial quantities of material if E/Z ratios are near unity. Use of ethylene can also cause adventitious olefin isomerization- A particularly serious problem when the E-alkene is energetically less favoured. Here, we show that dienes containing an E-alkenyl-B(pinacolato) group, widely used in catalytic cross-coupling, possess the requisite electronic and steric attributes to allow them to be converted stereoselectively to E-macrocyclic alkenes. The reaction is promoted by a molybdenum monoaryloxide pyrrolide complex and affords products at a yield of up to 73 per cent and an E/Z ratio greater than 98/2. We highlight the utility of the approach by preparing recifeiolide (a 12-membered-ring antibiotic) and pacritinib (an 18-membered-ring enzyme inhibitor), the Z-isomer of which is less potent than the E-isomer. Notably, the 18-membered-ring moiety of pacritinib- A potent anti-cancer agent that is in advanced clinical trials for treating lymphoma and myelofibrosis-was prepared by RCM carried out at a substrate concentration 20 times greater than when a ruthenium carbene was used.National Institutes of Health (U.S.) (Grant GM-59426)National Science Foundation (U.S.) (Grant CHE-1362763

Benthic macroinvertebrate assemblages in remediated wetlands around Sydney, Australia

To investigate potential high organisational level impacts of persistent organic pollution in the wetlands in the Sydney Olympic Park (SOP) remediated site, the benthic macroinvertebrate assemblages of seven wetlands within SOP and two off-site reference wetlands were examined. Sediment cores were collected, stained and preserved from each study site and the macroinvertebrates identified to the appropriate taxonomic level (Class, Order, Family, Subfamily). Data were analysed for taxon richness and macroinvertebrate abundance and multivariate techniques were used to identify chemical/physical characteristics of the sediment, which were important influences on the differences in the assemblage between study sites. Macroinvertebrate abundance was highly variable between study sites and taxon richness was low across all sites. Oligochaetes, nematodes, ostracods and chironomids were the most common taxa found and were the most important in influencing differences between the macroinvertebrate assemblages among the study sites.Sediment grain size and chemical characteristics of the sediments (ΣPAH, ΣPCB, TCDDeq and heavy metal concentrations) were important in separating the study sites based on taxon richness and abundance. Canonical correspondence analysis separated the macroinvertebrate assemblages at newly two created wetlands from those at other study sites including the urban reference sites. Increased sediment POP contamination (particularly as measured TCDDeq and ΣDDT concentrations) is a likely contributor in excluding pollution sensitive taxa and, therefore, alterations to benthic macroinvertebrate assemblages. Further, the influence of TOC suggests the significance of catchment inputs in contributing to changes in macroinvertebrate assemblage. The SOP remediation led to the establishment of wetlands with benthic communities representative of those expected in urban wetlands