Allylboration of carbonyl compounds is one of the most widely used methods in the stereoselective synthesis of natural products. However, these powerful transformations are so far limited to allyl- ...or crotylboron reagents; ring-strained substituents in the α-position have not been investigated. Such substrates would lead to an increase in strain energy upon allylboration and as such cause a significant increase in the activation barrier of the reaction. Indeed, no reaction was observed between an α-cyclopropyl allylboronic ester and an aldehyde. However, by converting the boronic ester into the much more reactive borinic ester, the allylboration proceeded well giving alkylidenecyclopropanes in high yield. This process was highly diastereoselective and gives rapid access to versatile alkylidenecyclopropanes and alkylidenecyclobutanes. The chemistry shows a broad substrate scope in terms of both the range of vinylcycloalkyl boronic esters and aldehydes that can be employed. The intermediate boronate complexes were also found to be potent nucleophiles, reacting with a range of non-carbonyl-based electrophiles and radicals, leading to an even broader range of alkylidenecyclopropanes and alkylidenecyclobutanes. Using 11B NMR experiments, we were able to track the intermediates involved, and DFT calculations supported the experimental findings.
We present results of a search for late-time radio emission and fast radio bursts (FRBs) from a sample of type-I superluminous supernovae (SLSNe-I). We used the Karl G. Jansky Very Large Array to ...observe 10 SLSN-I more than 5 yr old at a frequency of 3 GHz. We searched fast-sampled visibilities for FRBs and used the same data to perform a deep imaging search for late-time radio emission expected in models of magnetar-powered supernovae. No FRBs were found. One SLSN-I, PTF10hgi, is detected in deep imaging, corresponding to a luminosity of 1.2 × 1028 erg s−1. This luminosity, considered with the recent 6 GHz detection of PTF10hgi in Eftekhari et al., supports the interpretation that it is powered by a young, fast-spinning (∼ms spin period) magnetar with ∼15 M of partially ionized ejecta. Broadly, our observations are most consistent with SLSNe-I being powered by neutron stars with fast spin periods, although most require more free-free absorption than is inferred for PTF10hgi. We predict that radio observations at higher frequencies or in the near future will detect these systems and begin constraining properties of the young pulsars and their birth environments.
The reaction of sulfur ylides with carbonyl compounds to give epoxides is an important synthetic method. This Account charts the recent advances in rendering this process both asymmetric and ...catalytic. Two catalytic methods have been developed: the first involving the reaction of a sulfide with an alkyl halide in the presence of a base and aldehyde and the second involving the reaction of a sulfide with a diazo compound or diazo precursor in the presence of a metal catalyst and aldehyde. These catalytic methods coupled with suitable chiral sulfides provide a new catalytic asymmetric epoxidation process for the preparation of epoxides. The scope of the two catalytic processes is discussed together with the factors that influence both relative and absolute stereochemistry. The application of these methods in target-orientated synthesis is also reviewed.
There are a limited number of ring‐contraction methodologies which convert readily available five‐membered rings into strained four‐membered rings. Here we report a photo‐induced radical‐mediated ...ring contraction of five‐membered‐ring alkenyl boronate complexes into cyclobutanes. The process involves the addition of an electrophilic radical to the electron‐rich alkenyl boronate complex, leading to an α‐boryl radical. Upon one‐electron oxidation, ring‐contractive 1,2‐metalate rearrangement occurs to give a cyclobutyl boronic ester. A range of radical precursors and vinyl boronates can be employed, and chiral cyclobutanes can be accessed with high levels of stereocontrol. The process was extended to the preparation of benzofused cyclobutenes and the versatility of the boronic ester was demonstrated by conversion to other functional groups.
React to contract: Easily accessible cyclic vinyl boronate complexes undergo a strain‐increase ring contraction through a reaction with electrophilic radicals generated by visible light. A variety of cyclobutyl boronic esters can be obtained in high yields and with excellent stereocontrol, including those containing contiguous quaternary stereocenters and also substantially more strained benzofused cyclobutenes.
Oncogenic activation of RAS genes via point mutations occurs in 20%–30% of human cancers. The development of effective RAS inhibitors has been challenging, necessitating new approaches to inhibit ...this oncogenic protein. Functional studies have shown that the switch region of RAS interacts with a large number of effector proteins containing a common RAS-binding domain (RBD). Because RBD-mediated interactions are essential for RAS signaling, blocking RBD association with small molecules constitutes an attractive therapeutic approach. Here, we present evidence that rigosertib, a styryl-benzyl sulfone, acts as a RAS-mimetic and interacts with the RBDs of RAF kinases, resulting in their inability to bind to RAS, disruption of RAF activation, and inhibition of the RAS-RAF-MEK pathway. We also find that rigosertib binds to the RBDs of Ral-GDS and PI3Ks. These results suggest that targeting of RBDs across multiple signaling pathways by rigosertib may represent an effective strategy for inactivation of RAS signaling.
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•Rigosertib binds to the RAS-binding domains (RBDs) of multiple RAS effectors•Binding of rigosertib to RAF-RBD inhibits RAS-RAF interaction and impairs the kinase•Rigosertib inhibits MEK-ERK pathway activated by growth factors and oncogenic RAS
Binding of a small molecule to the conserved RAS-binding domain of RAF prevents its functional association with RAS and impairs tumorigenic proliferation.
The idea that signal-dependent transcription might involve the generation of transient DNA nicks or even breaks in the regulatory regions of genes, accompanied by activation of DNA damage repair ...pathways, would seem to be counterintuitive, as DNA damage is usually considered harmful to cellular integrity. However, recent studies have generated a substantial body of evidence that now argues that programmed DNA single- or double-strand breaks can, at least in specific cases, have a role in transcription regulation. Here, we discuss the emerging functions of DNA breaks in the relief of DNA torsional stress and in promoter and enhancer activation.
The energy costs have increased substantially in recent years due to widespread development in India. Vast agro and animal waste resources are available which can easily be harnessed for biogas ...production economically Recently, there has been a renewed interest to revive the National biogas programme to meet the ever-increasing energy demand. India has set a target of reducing oil imports by 10% through the increased use of natural gas contribution in the current energy mix of 6.5%–15% by 2022. In this study the new Indian biogas policy initiatives for biogas production, new plant designs are presented along with a comparative analysis of the policy with similar policies of selected countries. The flaws in the past implementation of Indian bio-gas programmes, biogas technology as per most recent data along with identifying gaps in the new Indian biogas policy, are presented. A strategy is outlined to utilize large quantities of available food, agro and animal waste resources for a sustainable bio-gas policy as per UN sustainable development goal numbers 1, 7 and 13. The need for a sustainable biogas policy is emphasized to provide a clean fuel for cooking, heating, and lighting with focus on rural poor worldwide.
Strategy for a novel sustainable bio-gas policyThe flaws in the past implementation of Indian bio-gas programmes, current status of biogas technology as per most recent data along with identifying gaps in the new Indian biogas policy, are presented. Based on the comparative analysis of new Indian policy with similar policies of selected countries, a strategy is outlined to utilize vast quantities of available agro, food and animal resources for a sustainable bio-gas policy as per UN sustainable development goal numbers 1, 7 and 13, to provide clean bio-gas fuel to the poor worldwide. Display omitted
•New Indian Biogas Policy Perspectives are presented.•Biogas policies of selected countries are critically analyzed. .•Policy concerns of propagating liquid petroleum gas in rural areas, are identified.•Strategy is outlined for effective implementation of new sustainable biogas policy.
Developing crops that are better adapted to abiotic stresses is important for food production in many parts of the world today. Anticipated changes in climate and its variability, particularly ...extreme temperatures and changes in rainfall, are expected to make crop improvement even more crucial for food production. Here, we review two key biotechnology approaches, molecular breeding and genetic engineering, and their integration with conventional breeding to develop crops that are more tolerant of abiotic stresses. In addition to a multidisciplinary approach, we also examine some constraints that need to be overcome to realize the full potential of agricultural biotechnology for sustainable crop production to meet the demands of a projected world population of nine billion in 2050.
There is significant interest in using hydrogen and natural gas for enhancing the performance of diesel engines. We report herein a numerical investigation on the ignition of
n-C
7H
16/H
2 and
n-C
7H
...16/CH
4 fuel blends. The CHEMKIN 4.1 software is used to model ignition in a closed homogenous reactor under conditions relevant to diesel/HCCI engines. Three reaction mechanisms used are (i) NIST mechanism involving 203 species and 1463 reactions, (ii) Dryer mechanism with 116 species and 754 reactions, and (iii) a reduced mechanism (Chalmers) with 42 species and 168 reactions. The parameters include pressures of 30 atm and 55 atm, equivalence ratios of
ɸ = 0.5, 1.0 and 2.0, temperature range of 800–1400 K, and mole fractions of H
2 or CH
4 in the blend between 0 and 100%. For
n-C
7H
16/air mixtures, the Chalmers mechanism not only provides closer agreement with measurements compared to the other two mechanisms, but also reproduces the negative temperature coefficient regime. Consequently, this mechanism is used to characterize the effects of H
2 or CH
4 on the ignition of
n-C
7H
16. Results indicate that H
2 or CH
4 addition has a relatively small effect on the ignition of
n-C
7H
16/air mixtures, while the
n-C
7H
16 addition even in small amount modifies the ignition of H
2/air and CH
4/air mixtures significantly. The
n-C
7H
16 addition decreases and increases the ignition delays of H
2/air mixtures at low and high temperatures, respectively, while its addition to CH
4/air mixtures decreases ignition delays at all temperatures. The sensitivity analysis indicates that ignition characteristics of these fuel blends are dominated by the pyrolysis/oxidation chemistry of
n-heptane, with heptyl (C
7H
16-2) and hydoxyl (OH) radicals being the two most important species.
► A computational study on the ignition of hydrogen–heptane and methane–heptane blends at engine conditions. ► A detailed mechanism fully validated against
n-heptane, methane, and hydrogen ignition data at high pressures. ► Addition of hydrogen or methane has a relatively small effect on the ignition of
n-heptane. ► Addition of
n-heptane has a significant effect on the ignition of hydrogen or methane. ► Sensitivity study performed to identify important reactions and species for the ignition of fuel blends.
In recent times, waste management has emerged as a significant environmental challenge, and sewage is among the major contributors due to the rapidly increasing population. Despite sewage treatment ...plants (STPs) being the solution for the treatment of sewage, they have been identified as sources of greenhouse gas (GHG) emissions. This study aimed to estimate the contribution of STPs to GHG emissions in the state. This was achieved by visiting the sites, filling scientifically designed questionnaires, sample collection as well as computational methods by Intergovernmental Panel on Climate Change. The assessment of direct and indirect emissions from the STPs revealed that emissions were caused by the activated sludge process, electricity consumption, transportation, and sludge storage. Electricity consumption by STPs was responsible for the highest emissions, accounting for 43% of the total emissions, equivalent to 20,823 tCO
eq. The activated sludge process contributed 31% (14,934 tCO
eq) of the emissions, while storage of sludge in landfills accounted for 24% (11,359 tCO
eq). Additionally, transportation contributed 2% (1121 tCO
eq) of the emissions. In total, the STPs in Himachal Pradesh had the potential to contribute 48,237 tCO
eq GHG emissions annually. Thus, the study suggests process-level modifications in STPs of Himachal Pradesh to mitigate GHG emissions. This research provides insight into the GHG emissions from STPs and highlights the need for their management to reduce environmental impacts.
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