The asymmetric alkylation of enolates is a particularly versatile method for the construction of α-stereogenic carbonyl motifs, which are ubiquitous in synthetic chemistry. Over the past several ...decades, the focus has shifted to the development of new catalytic methods that depart from classical stoichiometric stereoinduction strategies (e.g., chiral auxiliaries, chiral alkali metal amide bases, chiral electrophiles, etc.). In this way, the enantioselective alkylation of prochiral enolates greatly improves the step- and redox-economy of this process, in addition to enhancing the scope and selectivity of these reactions. In this review, we summarize the origin and advancement of catalytic enantioselective enolate alkylation methods, with a directed emphasis on the union of prochiral nucleophiles with carbon-centered electrophiles for the construction of α-stereogenic carbonyl derivatives. Hence, the transformative developments for each distinct class of nucleophile (e.g., ketone enolates, ester enolates, amide enolates, etc.) are presented in a modular format to highlight the state-of-the-art methods and current limitations in each area.
The transition metal-catalyzed allylic substitution reaction is a particularly versatile method for the construction of carbon–carbon and carbon–heteroatom bonds. In this regard, the ...rhodium-catalyzed variant has emerged as a powerful method for the regioselective and stereospecific allylic substitution of chiral nonracemic secondary and tertiary allylic carbonates with a variety of carbon- and heteroatom-based nucleophiles. In addition, recent developments have made the analogous enantioselective process possible using prochiral nucleophiles with achiral allylic electrophiles, which represents a significant advance in this area. In this Perspective, the discovery, development and applications of these conceptually orthogonal strategies to target-directed synthesis are discussed, with a particular emphasis given to those methods developed in our laboratory.
Abstract
Drylands cover 41% of the earth’s land surface and include 45% of the world’s agricultural land. These regions are among the most vulnerable ecosystems to anthropogenic climate and land use ...change and are under threat of desertification. Understanding the roles of anthropogenic climate change, which includes the CO
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fertilization effect, and land use in driving desertification is essential for effective policy responses but remains poorly quantified with methodological differences resulting in large variations in attribution. Here, we perform the first observation-based attribution study of desertification that accounts for climate change, climate variability, CO
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fertilization as well as both the gradual and rapid ecosystem changes caused by land use. We found that, between 1982 and 2015, 6% of the world’s drylands underwent desertification driven by unsustainable land use practices compounded by anthropogenic climate change. Despite an average global greening, anthropogenic climate change has degraded 12.6% (5.43 million km
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) of drylands, contributing to desertification and affecting 213 million people, 93% of who live in developing economies.
The egg's blocks to polyspermy (fertilization of an egg by more than one sperm) were originally identified in marine and aquatic species with external fertilization, but polyspermy matters in ...mammalian reproduction too. Embryonic triploidy is a noteworthy event associated with pregnancy complications and loss. Polyspermy is a major cause of triploidy with up to 80% of triploid conceptuses being the result of dispermic fertilization. The mammalian female reproductive tract regulates the number of sperm that reach the site of fertilization, but mammals also utilize egg‐based blocks to polyspermy. The egg‐based blocks occur on the mammalian egg coat (the zona pellucida) and the egg plasma membrane, with apparent variation between different mammalian species regarding the extent to which one or both are used. The zona pellucida block to polyspermy has some similarities to the slow block in water‐dwelling species, but the mammalian membrane block to polyspermy differs substantially from the fast electrical block that has been characterized in marine and aquatic species. This review discusses what is known about the incidence of polyspermy in mammals and about the mammalian membrane block to polyspermy, as well as notes some lesser‐characterized potential mechanisms contributing to polyspermy prevention in mammals.
In the face of global urbanisation and climate change, scientists are increasingly using cities to experiment with more resilient forms of urban infrastructure. Experimentation represents the ...practical dimension of adaptation; it is what happens in practice when policymakers, researchers, businesses and communities are charged with finding new paths. This paper traces one particular lineage of experimentation to resilience ecology, which rejects the possibility of external control over a system, casting planning and administrative functions, and even scientists themselves, as part of a Social-Ecological System. Using insights from political ecology, laboratory studies and urban studies, the paper explores how ecologists involved with the Long Term Ecological Research Programme in the USA are embedding adaptive experiments into urban governance. Discussion focuses on the role of place in adaptive science, considering the political implications of ecologising urban governance and rendering it experimental.
This study examined the performance and future predictions for the Middle East produced by 18 global climate models participating in the Intergovernmental Panel on Climate Change Fourth Assessment ...Report. Under the Special Report on Emission Scenarios A2 emissions scenario the models predict an overall temperature increase of ~1.4 K by mid-century, increasing to almost 4 K by late-century for the Middle East. In terms of precipitation the southernmost portion of the domain experiences a small increase in precipitation due to the Northward movement of the Inter-Tropical Convergence Zone. The largest change however is a decrease in precipitation that occurs in an area covering the Eastern Mediterranean, Turkey, Syria, Northern Iraq, Northeastern Iran and the Caucasus caused by a decrease in storm track activity over the Eastern Mediterranean. Other changes likely to impact the region include a decrease of over 170,000 km² in viable rainfed agriculture land by late-century, increases in the length of the dry season that reduces the length of time that the rangelands can be grazed, and changes in the timing of the maximum precipitation in Northern Iran that will impact the growing season, forcing changes in cropping strategy or even crop types.
We present the 2SXPS (Swift-XRT Point Source) catalog, containing 206,335 point sources detected by the Swift X-ray Telescope (XRT) in the 0.3-10 keV energy range. This catalog represents a ...significant improvement over 1SXPS, with double the sky coverage (now 3790 deg2), and several significant developments in source detection and classification. In particular, we present for the first time techniques to model the effect of stray light-significantly reducing the number of spurious sources detected. These techniques will be very important for future, large effective area X-ray missions, such as the forthcoming Athena X-ray observatory. We also present a new model of the XRT point-spread function and a method for correctly localizing and characterizing piled-up sources. We provide light curves-in four energy bands, two hardness ratios, and two binning timescales-for every source, and from these deduce that over 80,000 of the sources in 2SXPS are variable in at least one band or hardness ratio. The catalog data can be queried or downloaded via a web interface at https://www.swift.ac.uk/2SXPS, via HEASARC, or in Vizier (IX/58).
In this study, the androgen-receptor inhibitor enzalutamide improved progression-free and overall survival in men with castration-resistant metastatic prostate cancer who had not received ...chemotherapy.
Prostate cancer is the most commonly diagnosed cancer and the sixth leading cause of cancer-related death among men worldwide.
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Strategies to block androgen-receptor signaling have formed the backbone of prostate-cancer therapy since the first description of the hormonal dependence of this cancer in 1941.
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Advances in endocrine therapies have improved survival in men with high-risk locoregional prostate cancer.
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,
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However, new hormonal agents have been shown to extend survival in men with metastatic castration-resistant disease.
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–
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In most patients who are treated for advanced recurrent prostate cancer with androgen-deprivation therapy (comprising a luteinizing hormone–releasing hormone LHRH analogue or orchiectomy with . . .
Summary
Background
The incidence of acute pancreatitis has increased sharply in many European countries and the USA in recent years.
Aim
To establish trends in incidence and mortality for acute ...pancreatitis in Wales, UK, and to assess how incidence may be linked to factors including social deprivation, seasonal effects and alcohol consumption.
Methods
Use of record linked inpatient, mortality and primary care data for 10 589 hospitalised cases of acute pancreatitis between 1999 and 2010.
Results
The incidence of acute pancreatitis was 30.0 per 100 000 population overall, mortality was 6.4% at 60 days. Incidence increased significantly from 27.6 per 100 000 in 1999 to 36.4 in 2010 (average annual increase = 2.7% per year), there was little trend in mortality (0.2% average annual reduction). The largest increases in incidence were among women aged <35 years (7.9% per year) and men aged 35–44 (5.7%) and 45–54 (5.3%). Incidence was 1.9 times higher among the most deprived quintile of patients compared with the most affluent (3.9 times higher for alcoholic acute pancreatitis and 1.5 for gallstone acute pancreatitis). Acute pancreatitis was increased significantly during the Christmas and New Year weeks by 48% (95% CI = 24–77%) for alcoholic aetiology, but not for gallstone aetiology (9%). Alcoholic admissions were increased with higher consumption of spirits and beer, but not wine.
Conclusions
The study shows an elevated rate of alcoholic acute pancreatitis during the Christmas and New Year period. Acute pancreatitis continues to rise, most rapidly for young women, while alcoholic acute pancreatitis is linked strongly with social deprivation.
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