Search

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An operationally simple in situ protection/deprotection strategy that significantly expands the scope of kinetically controlled catalytic Z‐ and E‐selective olefin metathesis is introduced. Prior to the addition of a sensitive Mo‐ or Ru‐based complex, treatment of a hydroxy‐ or a carboxylic‐acid‐containing olefin with commercially available HB(pin) or readily accessible HB(trip)2 (pin=pinacolato, trip=2,4,6‐tri(isopropyl)phenyl) for 15 min is sufficient for efficient generation of a desired product. Routine workup leads to quantitative deprotection. A range of stereochemically defined Z‐ and E‐alkenyl chlorides, bromides, fluorides, and boronates or Z‐trifluoromethyl‐substituted alkenes with a hydroxy or carboxylic acid group were thus prepared in 51–97 % yield with 93 to >98 % stereoselectivity. We also show that, regardless of whether a polar functional unit is present or not, a small amount of HB(pin) may be used to remove residual water, significantly enhancing efficiency. Without a trace: Alkenes containing a hydroxy and/or a carboxylic acid group were converted into Z or E alkenes through one‐pot operations consisting of in situ protection, catalytic cross‐metathesis, and deprotection by mild workup/purification. Prior to the addition of a sensitive Mo or Ru complex, treatment of the olefin with HB(pin) or readily available HB(trip)2 for 15 min was sufficient for the efficient generation of a desired product (see scheme). [ABSTRACT FROM AUTHOR]

Catalytic cross-metathesis is a central transformation in chemistry, yet corresponding methods for the stereoselective generation of acyclic trisubstituted alkenes in either the E or the Z isomeric forms are not known. The key problems are a lack of chemoselectivity-namely, the preponderance of side reactions involving only the less hindered starting alkene, resulting in homo-metathesis by-products-and the formation of short-lived methylidene complexes. By contrast, in catalytic cross-coupling, substrates are more distinct and homocoupling is less of a problem. Here we show that through cross-metathesis reactions involving E- or Z-trisubstituted alkenes, which are easily prepared from commercially available starting materials by cross-coupling reactions, many desirable and otherwise difficult-to-access linear E- or Z-trisubstituted alkenes can be synthesized efficiently and in exceptional stereoisomeric purity (up to 98 per cent E or 95 per cent Z). The utility of the strategy is demonstrated by the concise stereoselective syntheses of biologically active compounds, such as the antifungal indiacen B and the anti-inflammatory coibacin D. [ABSTRACT FROM AUTHOR]

The development of catalyst-controlled stereoselective olefin metathesis processes has been a pivotal recent advance in chemistry. The incorporation of appropriate ligands within complexes based on molybdenum, tungsten and ruthenium has led to reactivity and selectivity levels that were previously inaccessible. Here we show that molybdenum monoaryloxide chloride complexes furnish higher-energy (Z) isomers of trifluoromethyl-substituted alkenes through cross-metathesis reactions with the commercially available, inexpensive and typically inert Z-1,1,1,4,4,4-hexafluoro-2-butene. Furthermore, otherwise inefficient and non-stereoselective transformations with Z-1,2-dichloroethene and 1,2-dibromoethene can be effected with substantially improved efficiency and Z selectivity. The use of such molybdenum monoaryloxide chloride complexes enables the synthesis of representative biologically active molecules and trifluoromethyl analogues of medicinally relevant compounds. The origins of the activity and selectivity levels observed, which contradict previously proposed principles, are elucidated with the aid of density functional theory calculations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Isolates of recently spreading races of yellow rust from wheat and triticale in Europe were analysed using virulence phenotypic data of 2605 isolates sampled in 12 countries between 2000 and 2014. A subset of 239 isolates was investigated by microsatellite markers. At least three races of non-European origin, termed 'Warrior', 'Kranich' and 'Triticale aggressive', were identified in the post-2011 population. The Warrior race was already present in high frequencies in the first year of detection in most European countries and to a large extent it replaced the pre-2011 European population. In contrast, the two other exotic races were localized to certain regions and/or crop type. The presence already of at least six multilocus genotypes of the Warrior race and five genotypes of the Kranich race in the first year of detection and across large areas is consistent with a hypothesis of aerial spread from genetically diverse source populations. A comparison with reference isolates sampled from six continents suggested that the Warrior and Kranich races originated from sexually recombining populations in the centre of diversity of the yellow rust fungus in the near-Himalayan region of Asia. However, the Triticale aggressive race was most similar to populations in the Middle East/Central Asia. The study illustrated the potential role of sexual Puccinia striiformis populations as a reservoir for new races replacing distant clonal populations. [ABSTRACT FROM AUTHOR]

A unique collection of spore samples of Puccinia striiformis, often referred to as the 'Stubbs collection', has been stored in liquid nitrogen from 18 to 45 years. A subset of samples representing 35 countries and 28 years was investigated to assess recovery rate, race identity and previously undetected virulence. A new method for recovery using an airbrush sprayer and Novec™ 7100 for inoculating the host plants was highly successful. Ninety-six percent of 231 isolates were recovered. Virulence phenotyping was done using differential sets of wheat genotypes representing specific-resistance genes. A total of 181 samples represented single genotypes (isolates), whereas 40 samples consisted of at least two genotypes. Race identity was confirmed for 102 of 181 single-genotype isolates. The virulence phenotype was updated for additional 44 isolates based on improved resolution of results because of updated and more informative wheat-differential sets. The remaining 35 isolates showed discrepancies for one or more virulences when compared with past results. Additional virulences corresponding to Yr17, Yr25 and Yr27, respectively, which were not assayed originally, were discovered. The value of biological collections for research and plant breeding is discussed along with the challenges of maintaining collections of biotrophic microorganisms. [ABSTRACT FROM AUTHOR]

Importance Medication computerised provider order entry (CPOE) has been shown to decrease errors and is being widely adopted. However, CPOE also has potential for introducing or contributing to errors. Objectives The objectives of this study are to (a) analyse medication error reports where CPOE was reported as a 'contributing cause' and (b) develop 'use cases' based on these reports to test vulnerability of current CPOE systems to these errors. Methods A review of medication errors reported to United States Pharmacopeia MEDMARX reporting system was made, and a taxonomy was developed for CPOE-related errors. For each error we evaluated what went wrong and why and identified potential prevention strategies and recurring error scenarios. These scenarios were then used to test vulnerability of leading CPOE systems, asking typical users to enter these erroneous orders to assess the degree to which these problematic orders could be entered. Results Between 2003 and 2010, 1.04 million medication errors were reported to MEDMARX, of which 63 040 were reported as CPOE related. A review of 10 060 CPOE-related cases was used to derive 101 codes describing what went wrong, 67 codes describing reasons why errors occurred, 73 codes describing potential prevention strategies and 21 codes describing recurring error scenarios. Ability to enter these erroneous order scenarios was tested on 13 CPOE systems at 16 sites. Overall, 298 (79.5%) of the erroneous orders were able to be entered including 100 (28.0%) being 'easily' placed, another 101 (28.3%) with only minor workarounds and no warnings. Conclusions and relevance Medication error reports provide valuable information for understanding CPOE-related errors. Reports were useful for developing taxonomy and identifying recurring errors to which current CPOE systems are vulnerable. Enhanced monitoring, reporting and testing of CPOE systems are important to improve CPOE safety. [ABSTRACT FROM AUTHOR]

This study assessed the effects of exposure to air pollution on hospitalization for acute lower respiratory infection (ALRI) among children under 5 years of age in Ho Chi Minh City (HCMC) from 2003 to 2005. Case-crossover analyses with time-stratified selection of control periods were conducted using daily admissions for pneumonia and bronchiolitis and daily, citywide averages of PM, NO, SO, and O (8-h maximum average) estimated from the local air quality monitoring network. Increased concentrations of NO and SO were associated with increased admissions in the dry season (November to April), with excess risks of 8.50% (95%CI 0.80-16.79) and 5.85% (95%CI 0.44-11.55), respectively. PM could also be associated with increased admissions in the dry season, but high correlation between PM and NO (0.78) limits our ability to distinguish between PM and NO effects. In the rainy season (May-October), negative associations between pollutants and admissions were observed. Results of this first study of the health effects of air pollution in HCMC support the presence of an association between combustion-source pollution and increased ALRI admissions. ALRI admissions were generally positively associated with ambient levels of PM, NO, and SO during the dry season, but not the rainy season. Negative results in the rainy season could be driven by residual confounding present from May to October. Preliminary exploratory analyses suggested that seasonal differences in the prevalence of viral causes of ALRI could be driving the observed differences in effects by season. [ABSTRACT FROM AUTHOR]

Background: Information on life expectancy (LE) change is of great concern for policy makers, as evidenced by discussions of the "harvesting" (or "mortality displacement") issue, i.e. how large an LE loss corresponds to the mortality results of time series (TS) studies. Whereas loss of LE attributable to chronic air pollution exposure can be determined from cohort studies, using life table methods, conventional TS studies have identified only deaths due to acute exposure, during the immediate past (typically the preceding one to five days), and they provide no information about the LE loss per death.Methods: We show how to obtain information on population-average LE loss by extending the observation window (largest "lag") of TS to include a sufficient number of "impact coefficients" for past exposures ("lags"). We test several methods for determining these coefficients. Once all of the coefficients have been determined, the LE change is calculated as time integral of the relative risk change after a permanent step change in exposure.Results: The method is illustrated with results for daily data of non-accidental mortality from Hong Kong for 1985 - 2005, regressed against PM10 and SO2 with observation windows up to 5 years. The majority of the coefficients is statistically significant. The magnitude of the SO2 coefficients is comparable to those for PM10. But a window of 5 years is not sufficient and the results for LE change are only a lower bound; it is consistent with what is implied by other studies of long term impacts.Conclusions: A TS analysis can determine the LE loss, but if the observation window is shorter than the relevant exposures one obtains only a lower bound. [ABSTRACT FROM AUTHOR]

Cervical cancer incidence and mortality statistics in Hong Kong during 1972-2001 were examined to estimate the potential number of cancer cases that can be averted and years of life saved after the launch of an organised, population-based cytologic screening recall programme in 2004 with projections to 2016. Incidence rates under the status quo of opportunistic screening were projected by an age-period-cohort model, using maximum likelihood and Bayesian methods. Modelled rates were translated into numbers of cancer cases and deaths using mid-year population figures and age-period-specific mortality to incidence ratios. We applied International Agency for Research on Cancer risk reduction estimates for different screening strategies to these base case figures to estimate the number of incident cancers potentially averted and years of life saved attributable to organised screening incremental to the current status quo. The estimated numbers of cases projected to be preventable by the maximum likelihood (Bayesian) approach from 2002 to 2016 were 4226 (4176), 3778 (3728) and 2334 (2287) with organised screening every 1, 3 and 5 years, compared to haphazard screening currently. Correspondingly, 33,000 (32,800), 29,500 (29,300) and 18,200 (17,900) years of life could potentially be saved. [ABSTRACT FROM AUTHOR]

Neonatal hypoglycemia represents an emergency of heterogeneous etiology. The occurrence of persistent hypoglycemia caused by hyperinsulinism has not been well established. Some authors claim that it may be more common than previously suggested. The diagnostic goal is to distinguish hyperinsulinemia from other causes of hypoglycemia because management strategies differ. The diagnosis of persistent hypoglycemia attributable to hyperinsulinism is made when insulin secretion is excessive or inappropriate (> 10 microIU/ml). Medical management includes frequent feeding, high hydrocarbon intake, glucagon, diazoxide, somatostatin or steroid treatment. In case of resistance to medical intervention, surgery consisting of subtotal pancreatectomy is performed to avoid neurological sequelae. However, pediatric organic hypoglycemia secondary to hyperinsulinism can be caused by either diffuse or focal pancreatic lesions. Differentiation between these two types of lesion is necessary since partial pancreatectomy can prevent diabetes. In this prospective study, pancreatic venous sampling (PVS) was evaluated for the preoperative localization of lesions in 25 children with hyperinsulinism and correlated with surgical, pathological and clinical outcome. PVS is the most accurate preoperative technique for localizing focal lesions in children. Besides being safe and effective, it has the great advantage of detecting focal secretion, thus reducing the need for extensive surgery. [ABSTRACT FROM AUTHOR]

Presents corrections to the article 'Trends in Breast Cancer Incidence in Hong Kong Between 1973 and 1999: An Age-Period-Cohort Analysis,' published in the 2002 issue of 'British Journal of Cancer.'