Evaluating polymer-supported isothiourea catalysis in industrially-preferable solvents for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols in batch and flow

The authors thank the Royal Society and the Science and Engineering Board of India (SERB) for the award of a Royal Society-SERB Newton International Fellowship (N.R.G.). The authors also thank the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, grant code EP/L016419/1, R.M.N.P.) for funding. Financial support from the EPSRC (EP/K000411/1) is gratefully acknowledged (R.C.). The authors thank the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) ERC grant agreement no. 279850 (A.D.S). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. C.R.-E. and M.A.P. acknowledge the financial support from CERCA Programme/Generalitat de Catalunya, MINECO (CTQ2015-69136-R, AEI/MINECO/FEDER, UE and Severo Ochoa Excellence Accreditation 2014–2018, SEV-2013-0319) and DEC Generalitat de Catalunya (Grant 2014SGR827).Polymer-supported Lewis base catalysts, based on the homogeneous isothioureas HyperBTM and BTM, have been synthesised and applied for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols. In batch, the use of industrially-preferable solvents was investigated, with dimethyl carbonate proving to be most generally-applicable. Significantly, the HyperBTM-derived immobilised catalysts were readily recycled, with no loss in either activity or selectivity. In addition to the kinetic resolution of secondary benzylic, propargylic, allylic and cycloalkanol derivatives, a range of 21 tertiary heterocyclic alcohols, based on privileged 3-hydroxyoxindole and 3-hydroxypyrrolidinone substructures, were resolved with up to excellent selectivity (s = 7–190). Finally, the immobilised isothiourea catalysts were applied in a packed bed reactor to demonstrate the first example of the kinetic resolution of tertiary heterocyclic alcohols in a continuous flow process. High selectivities were obtained for the resolution of 3-hydroxyoxindole derivatives in ethyl acetate (s up to 70); and for 3-hydroxypyrrolidinones derivatives in toluene (s up to 42).PostprintPeer reviewe

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

Background: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. Methods: This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. Discussion: This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country

Development of C2-Symmetric Chiral Bifunctional Triamines: Synthesis and Application in Asymmetric Organocatalysis

The synthesis and application of a newly designed C2-symmetric chiral bifunctional triamine family (C2-CBT) is reported. These enantiopure chiral triamine scaffolds can be accessed in multigram amounts from simple amino acids while avoiding chromatographic purification. As a proof of principle, C2-CBT has been studied in the aldol reaction of cyclic ketones with isatins, with the target tertiary alcohols being formed in a highly efficient manner. Catalyst recovery by simple extraction techniques and subsequent reuse has been performed

Self-Tuned Software-Managed Energy Reduction in Infiniband Links

One of the biggest challenges in high-performance computing is to reduce the power and energy consumption. Research in energy efficiency has focused mainly on energy consumption at the node level. Less attention has been given to the interconnect, which is becoming a significant source of energy-inefficiency. Although supercomputers undoubtedly require a high-performance interconnect, previous work has shown that network links have low average utilization. It is therefore possible to save energy using low-power modes, but link wake-up latencies must not lead to a loss in performance. This paper proposes the Self-tuned Pattern Prediction System (SPPS), a self-tuned algorithm for energy proportionality, which reduces interconnect energy consumption without needing any application-specific configuration parameters. The algorithm uses prediction to discover repetitive patterns in the application\u27s communication, and it is implemented inside the MPI library, so that existing MPI programs do not need to be modified. We build on previous work, which showed how the application structure can be successfully exploited to predict the communication idle intervals. The previous work, however, required the manual adjustment of a critical idle interval length, whose value depends on the application and has a major effect on energy savings. The new technique automatically discovers the optimal value of this parameter, resulting in a self-tuned algorithm that obtains large interconnect energy savings at little performance cost. We study the effectiveness of our approach using ten real applications and benchmarks. Our simulations show average energy savings in the network links of up to 21%. Moreover, the link wake-up latencies and additional computation times have a negligible effect on performance, with an average penalty less than 1%

ChemInform Abstract: Covalently Immobilized Tris(triazolyl)methanol-Cu(I) Complexes: Highly Active and Recyclable Catalysts for CuAAC Reactions.

Tris(1-benzyl-1H-1,2,3-triazol-4-yl)methanol (3), a highly efficient ligand for CuAAC reactions, has been immobilized onto Merrifield resins through different strategies. The S(N)2-supported Cu complex (8) is stable in water and under air; it is active at low catalyst loadings (1 mol%) and at low concentration (down to 0.125 M) in both aqueous and purely organic media. Resin 8 can be repeatedly reused in 1 : 1 MeOH-water for short reaction times (4 h) with the only precaution of Cu(I) reloading every five cycles

A Highly Active Catalyst for Huisgen 1,3-Dipolar Cycloadditions Based on the Tris(triazolyl)methanol-Cu(I) Structure

A new tris(1-benzyl-1H-1,2,3-triazol-4-yl)methanol ligand 3 has been prepared by a triple Cu(I)-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC). Ligand 3 forms a stable complex with CuCl, which catalyzes the Huisgen 1,3-dipolar cycloaddition on water or under neat conditions. Low catalyst loadings, short reaction times at room temperature, and compatibility with free amino groups make 3-CuCl an outstanding catalyst for CuAAC

Covalently immobilized tris(triazolyl) methanol-Cu(I) complexes: highly active and recyclable catalysts for CuAAC reactions

Tris(1-benzyl-1H-1,2,3-triazol-4-yl)methanol (3), a highly efficient ligand for CuAAC reactions, has been immobilized onto Merrifield resins through different strategies. The S(N)2-supported Cu complex (8) is stable in water and under air; it is active at low catalyst loadings (1 mol%) and at low concentration (down to 0.125 M) in both aqueous and purely organic media. Resin 8 can be repeatedly reused in 1 : 1 MeOH-water for short reaction times (4 h) with the only precaution of Cu(I) reloading every five cycles

Analyzing Performance Improvements and Energy Savings in Infiniband Architecture using Network Compression

One of the greatest challenges in HPC is total system power and energy consumption. Whereas HPC interconnects have traditionally been designed with a focus on bandwidth and latency, there is an increasing interest in minimising the interconnect\u27s energy consumption. This paper complements ongoing efforts related to power reduction and energy proportionality, by investigating the potential benefits from MPI data compression. We apply lossy compression to two common communication patterns in HPC kernels, in conjunction with recently introduced InfiniBand (IB) power saving modes. The results for the Alya CG kernel and Gromacs PME solver kernels show improvements in both performance and energy. While performance improvements are strongly influenced and changable depending on the type of communication pattern, energy savings in IB links are more consistent and proportional to achievable compression rates. We estimated an upper bound for link energy savings of up to 71% for the ALYA CG kernel, while for the Gromacs PME solver we obtained savings up to 63% compared to nominal energy when compression rate of 50% is used. We conclude that lossy compression is not always useful for performance improvements, but that it does reduce average IB link energy consumptio

Highly Functionalized Biaryls via Suzuki-Miyaura Cross-Coupling Catalyzed by Pd@MOF under Batch and Continuous Flow Regimes

A diverse set of more than 40 highly functionalized biaryls was synthesized successfully through the Suzuki-Miyaura cross-coupling reaction catalyzed by Pd nanoparticles supported in a functionalized mesoporous MOF (8 wt% Pd@MIL-101(Cr)-NH2). This could be achieved under some of the mildest conditions reported to date and a strong control over the leaching of metallic species could be maintained, despite the presence of diverse functional groups and/or several heteroatoms. Some of the targeted molecules are important intermediates in the synthesis of pharmaceuticals and we clearly exemplify the versatility of this catalytic system, which affords better yields than currently existing commercial procedures. Most importantly, Pd@MIL-101-NH2 was packed in a micro-flow reactor, which represents the first report of metallic nanoparticles supported on MOFs employed in flow chemistry for catalytic applications. A small library of 11 isolated compounds was created in a continuous experiment without replacing the catalyst, demonstrating the potential of the catalyst for large-scale applications.AuthorCount:8;</p