scholarly journals NaIO4/Br- as a mild system for the oxidation of 1-methyl-anthra-9,10-quinones

2015 ◽  
Author(s):  
Marcin Cybulski ◽  
Adam Formela ◽  
Katarzyna Sidoryk ◽  
Olga Michalak ◽  
Anna Rosa ◽  
...  
Keyword(s):  
High Pressure ◽  
Carboxylic Acids ◽  
Scale Up ◽  
Lithium Bromide ◽  
Cost Effective ◽  
Building Blocks ◽  
Multidrug Resistant ◽  
Resistant Cell ◽  
Direct Oxidation ◽  
Reaction Conditions

One of the anthraquinone classes comprises compounds with a carbonyl group. These natural or synthetic anthraquinones find their application as building blocks in the synthesis of the compounds with a biological activity. Recently, 4-substituted anthra-9,10-quinone-1-carboxylic acids (2) have been used as key intermediates in the synthesis of patented compounds (3) with anticancer activity against multidrug resistant cell lines. Although 2,7-dihydro-3H-dibenz[de,h]cinnolin-3,7-diones (3) were successfully synthetized in a small laboratory scale, several problems were observed during the preparation of their acid intermediates (2) in a multi-gram scale. The known methods for the preparation of 2 are based on the oxidation of the methyl group in anthra-9,10-quinones (1). The most common are: the oxidation with the diluted nitric acid under high pressure in a sealed tube at the temperature of 195-220 oC, the oxidation in nitrobenzene by passing chlorine gas through the reaction mixture at the temperature of 160-170 oC or in a presence of the fuming sulphuric acid. The mentioned methods require aggressive reagents and specific reaction conditions including high pressure and temperature. Thus, there was a need to find a new efficient, cost-effective and reproducible synthetic method of preparation of 2. While searching literature it was found that the direct oxidation of alkylarenes mediated by the sodium periodate/lithium bromide combination produces benzyl acetates throughout benzyl bromides in the acetic acid, or benzylic acids in the diluted inorganic acid. Based on these results we examined a variety of reaction conditions with or without the bromine source and the oxidizing anion. As a result, a novel procedure for the preparation of highly pure 4-substituted anthra-9,10-quinone-1-carboxylic acids (HPLC > 99.5%) using oxidizing anion/ brominating reagent system was developed. It enabled 2 isolation by the simple filtration of the reaction mixture and was applied in the scale-up of 2,7-dihydro-3H-dibenz[de,h]cinnolin-3,7-dione derivatives.

scholarly journals NaIO4/Br- as a mild system for the oxidation of 1-methyl-anthra-9,10-quinones

2015 ◽  
Author(s):  
Marcin Cybulski ◽  
Adam Formela ◽  
Katarzyna Sidoryk ◽  
Olga Michalak ◽  
Anna Rosa ◽  
...  
Keyword(s):  
High Pressure ◽  
Carboxylic Acids ◽  
Scale Up ◽  
Lithium Bromide ◽  
Cost Effective ◽  
Building Blocks ◽  
Multidrug Resistant ◽  
Resistant Cell ◽  
Direct Oxidation ◽  
Reaction Conditions

One of the anthraquinone classes comprises compounds with a carbonyl group. These natural or synthetic anthraquinones find their application as building blocks in the synthesis of the compounds with a biological activity. Recently, 4-substituted anthra-9,10-quinone-1-carboxylic acids (2) have been used as key intermediates in the synthesis of patented compounds (3) with anticancer activity against multidrug resistant cell lines. Although 2,7-dihydro-3H-dibenz[de,h]cinnolin-3,7-diones (3) were successfully synthetized in a small laboratory scale, several problems were observed during the preparation of their acid intermediates (2) in a multi-gram scale. The known methods for the preparation of 2 are based on the oxidation of the methyl group in anthra-9,10-quinones (1). The most common are: the oxidation with the diluted nitric acid under high pressure in a sealed tube at the temperature of 195-220 oC, the oxidation in nitrobenzene by passing chlorine gas through the reaction mixture at the temperature of 160-170 oC or in a presence of the fuming sulphuric acid. The mentioned methods require aggressive reagents and specific reaction conditions including high pressure and temperature. Thus, there was a need to find a new efficient, cost-effective and reproducible synthetic method of preparation of 2. While searching literature it was found that the direct oxidation of alkylarenes mediated by the sodium periodate/lithium bromide combination produces benzyl acetates throughout benzyl bromides in the acetic acid, or benzylic acids in the diluted inorganic acid. Based on these results we examined a variety of reaction conditions with or without the bromine source and the oxidizing anion. As a result, a novel procedure for the preparation of highly pure 4-substituted anthra-9,10-quinone-1-carboxylic acids (HPLC > 99.5%) using oxidizing anion/ brominating reagent system was developed. It enabled 2 isolation by the simple filtration of the reaction mixture and was applied in the scale-up of 2,7-dihydro-3H-dibenz[de,h]cinnolin-3,7-dione derivatives.

scholarly journals Direct detection of SARS-CoV-2 using non-commercial RT-LAMP reagents on heat-inactivated samples

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alisa Alekseenko ◽  
Donal Barrett ◽  
Yerma Pareja-Sanchez ◽  
Rebecca J. Howard ◽  
Emilia Strandback ◽  
...  
Keyword(s):  
Large Scale ◽  
Direct Detection ◽  
Dna Polymerases ◽  
Scale Up ◽  
Lamp Assay ◽  
Cost Effective ◽  
Reaction Conditions ◽  
Clinical Patient ◽  
Reverse Transcriptases ◽  
Large Scale Testing

AbstractRT-LAMP detection of SARS-CoV-2 has been shown to be a valuable approach to scale up COVID-19 diagnostics and thus contribute to limiting the spread of the disease. Here we present the optimization of highly cost-effective in-house produced enzymes, and we benchmark their performance against commercial alternatives. We explore the compatibility between multiple DNA polymerases with high strand-displacement activity and thermostable reverse transcriptases required for RT-LAMP. We optimize reaction conditions and demonstrate their applicability using both synthetic RNA and clinical patient samples. Finally, we validate the optimized RT-LAMP assay for the detection of SARS-CoV-2 in unextracted heat-inactivated nasopharyngeal samples from 184 patients. We anticipate that optimized and affordable reagents for RT-LAMP will facilitate the expansion of SARS-CoV-2 testing globally, especially in sites and settings where the need for large scale testing cannot be met by commercial alternatives.

scholarly journals Detection of SARS-CoV-2 using non-commercial RT-LAMP regents and raw samples.

2020 ◽  
Author(s):  
Alisa Alekseenko ◽  
Donal Barrett ◽  
Yerma Pareja-Sanchez ◽  
Rebecca Howard ◽  
Emilia Strandback ◽  
...  
Keyword(s):  
Dna Polymerases ◽  
Scale Up ◽  
Lamp Assay ◽  
Cost Effective ◽  
Economic Resources ◽  
Strand Displacement ◽  
Reaction Conditions ◽  
Clinical Patient ◽  
Displacement Activity ◽  
Reverse Transcriptases

RT-LAMP detection of SARS-CoV-2 has been shown as a valuable approach to scale up COVID-19 diagnostics and thus contribute to limiting the spread of the disease. Here we present the optimization of highly cost-effective in-house produced enzymes, and we benchmark their performance against commercial alternatives. We explore the compatibility between multiple DNA polymerases with high strand-displacement activity and thermostable reverse transcriptases required for RT-LAMP. We optimize reaction conditions and demonstrate their applicability using both synthetic RNA and clinical patient samples. Finally, we validated the optimized RT-LAMP assay for the detection of SARS-CoV-2 in raw nasopharyngeal samples from 184 patients. We anticipate that optimized and affordable reagents for RT-LAMP will facilitate the expansion of SARS-CoV-2 testing globally, especially in sites and settings with limited economic resources.

scholarly journals The Synthesis of Mannose-6-Phosphate Using Polyphosphate-Dependent Mannose Kinase

Catalysts ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 250
Author(s):  
Wenlong Zhu ◽  
Miaomiao Gao ◽  
Biqiang Chen ◽  
Tianwei Tan ◽  
Hui Cao ◽  
...  
Keyword(s):  
Scale Up ◽  
Enzymatic Reaction ◽  
Synthesis Method ◽  
Cost Effective ◽  
Industrial Applications ◽  
Key Factors ◽  
Reaction Conditions ◽  
Mannose 6 Phosphate ◽  
Arthrobacter Species ◽  
Optimal Reaction

Mannose-6-phosphate (M6P) is involved in many metabolic pathways in life, and it has important applications in the treatment of diseases. This study explored a cost-effective enzyme catalytic synthesis method of M6P, using polyphosphate-dependent mannose kinase from Arthrobacter species. This synthesis uses polyphosphate to replace expensive ATP, and it is greener and safer than chemical synthesis. This study investigated the effects of key factors such as metal ions, temperature, and substrate addition on this enzymatic reaction, and improved the conversion efficiency. We moreover take advantage of the response surface method to explore the best catalytic conditions synthetically. The conversion was 99.17% successful under the optimal reaction conditions. After a series of optimizations, we carried out a 200 mL scale-up experiment, which proved that the method has good prospects for industrial applications.

Synthetic Routes to Oxazolines

2019 ◽  
Vol 16 (6) ◽  
pp. 507-526
Author(s):  
Ensar Mulahmetovic ◽  
Gráinne C. Hargaden
Keyword(s):  
Zinc Oxide ◽  
Carboxylic Acids ◽  
Lewis Acids ◽  
Building Blocks ◽  
Hypervalent Iodine ◽  
Acid Catalysts ◽  
Triflic Acid ◽  
Lewis Acid Catalysts ◽  
Reaction Conditions ◽  
Synthetic Routes

In this mini-review, the main synthetic routes used in the preparation of oxazolines is presented. The review is systematically carried out and the syntheses are presented in terms of precursors utilised (nitriles, aldehydes and carboxylic acids). Additionally, the reported synthesis of all chiral and achiral oxazolines involve either the use of amino alcohols as essential building blocks or some form of intramolecular cyclisation reactions. A comparison of the effectiveness of various reaction initiators such as Lewis acids, bases, oxidants and metals as well as their respective reaction conditions is also described. Lewis acid catalysts such as zinc chloride, zinc oxide and indium (III) chloride as well as triflic acid and ruthenium complexes are presented as effective catalysts in the formation of oxazolines from nitrile precursors. Oxidising agents such as N-bromosuccinimide, hypervalent iodine reagents and reducing agents such as butyllithium have been used in the formation oxazolines from aldehydes. While carboxylic acids have been used effectively as good precursors to oxazolines when using reagents such as cyanuric chloride as well as transition metal containing catalysts such as copper, ruthenium and titanium. In some cases, catalyst free reaction conditions have also been reported offering substituted oxazolines through microwave and ultrasonic irradiation as well as under standard reflux conditions.

scholarly journals Toward scalable biocatalytic conversion of 5-hydroxymethylfurfural by galactose oxidase using coordinated reaction and enzyme engineering

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
William R. Birmingham ◽  
Asbjørn Toftgaard Pedersen ◽  
Mafalda Dias Gomes ◽  
Mathias Bøje Madsen ◽  
Michael Breuer ◽  
...  
Keyword(s):  
Production Efficiency ◽  
Cost Effective ◽  
Building Blocks ◽  
Enzyme Engineering ◽  
Galactose Oxidase ◽  
Reaction Conditions ◽  
Direct Preparation ◽  
The Cost ◽  
Further Development ◽  
Scalable Production

Abstract5-Hydroxymethylfurfural (HMF) has emerged as a crucial bio-based chemical building block in the drive towards developing materials from renewable resources, due to its direct preparation from sugars and its readily diversifiable scaffold. A key obstacle in transitioning to bio-based plastic production lies in meeting the necessary industrial production efficiency, particularly in the cost-effective conversion of HMF to valuable intermediates. Toward addressing the challenge of developing scalable technology for oxidizing crude HMF to more valuable chemicals, here we report coordinated reaction and enzyme engineering to provide a galactose oxidase (GOase) variant with remarkably high activity toward HMF, improved O2 binding and excellent productivity (>1,000,000 TTN). The biocatalyst and reaction conditions presented here for GOase catalysed selective oxidation of HMF to 2,5-diformylfuran offers a productive blueprint for further development, giving hope for the creation of a biocatalytic route to scalable production of furan-based chemical building blocks from sustainable feedstocks.

scholarly journals The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chathika K Weerasuriya ◽  
Rebecca C Harris ◽  
C Finn McQuaid ◽  
Fiammetta Bozzani ◽  
Yunzhou Ruan ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Second Line ◽  
Second Line Therapy ◽  
China And India ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Line Therapy ◽  
Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

A review of sustainable lignocellulose biorefining applying (natural) deep eutectic solvents (DESs) for separations, catalysis and enzymatic biotransformation processes

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Ana Bjelić ◽  
Brigita Hočevar ◽  
Miha Grilc ◽  
Uroš Novak ◽  
Blaž Likozar
Keyword(s):  
Special Section ◽  
Cost Effective ◽  
Deep Eutectic Solvents ◽  
Reaction Conditions ◽  
Co Catalysts ◽  
Biomass Fractionation ◽  
Functional Step ◽  
Natural Deep Eutectic Solvents ◽  
Economic Need ◽  
Molecular Compounds

AbstractConventional biorefinery processes are complex, engineered and energy-intensive, where biomass fractionation, a key functional step for the production of biomass-derived chemical substances, demands industrial organic solvents and harsh, environmentally harmful reaction conditions. There is a timely, clear and unmet economic need for a systematic, robust and affordable conversion method technology to become greener, sustainable and cost-effective. In this perspective, deep eutectic solvents (DESs) have been envisaged as the most advanced novel polar liquids that are entirely made of natural, molecular compounds that are capable of an association via hydrogen bonding interactions. DES has quickly emerged in various application functions thanks to a formulations’ simple preparation. These molecules themselves are biobased, renewable, biodegradable and eco-friendly. The present experimental review is providing the state of the art topical overview of trends regarding the employment of DESs in investigated biorefinery-related techniques. This review covers DESs for lignocellulosic component isolation, applications as (co)catalysts and their functionality range in biocatalysis. Furthermore, a special section of the DESs recyclability is included. For DESs to unlock numerous new (reactive) possibilities in future biorefineries, the critical estimation of its complexity in the reaction, separation, or fractionation medium should be addressed more in future studies.

scholarly journals A Sustainable Improvement of ω-Bromoalkylphosphonates Synthesis to Access Novel KuQuinones

Organics ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 107-117
Author(s):  
Mattia Forchetta ◽  
Valeria Conte ◽  
Giulia Fiorani ◽  
Pierluca Galloni ◽  
Federica Sabuzi
Keyword(s):  
Metal Oxides ◽  
Phosphonic Acid ◽  
Organic Molecules ◽  
Building Blocks ◽  
Reaction Conditions ◽  
Phosphonic Acids ◽  
Sustainable Improvement ◽  
Phosphonate Esters ◽  
First Time ◽  
Complex Organic

Owing to the attractiveness of organic phosphonic acids and esters in the pharmacological field and in the functionalization of conductive metal-oxides, the research of effective synthetic protocols is pivotal. Among the others, ω-bromoalkylphosphonates are gaining particular attention because they are useful building blocks for the tailored functionalization of complex organic molecules. Hence, in this work, the optimization of Michaelis–Arbuzov reaction conditions for ω-bromoalkylphosphonates has been performed, to improve process sustainability while maintaining good yields. Synthesized ω-bromoalkylphosphonates have been successfully adopted for the synthesis of new KuQuinone phosphonate esters and, by hydrolysis, phosphonic acid KuQuinone derivatives have been obtained for the first time. Considering the high affinity with metal-oxides, KuQuinones bearing phosphonic acid terminal groups are promising candidates for biomedical and photo(electro)chemical applications.

scholarly journals 2D-3D integration of hexagonal boron nitride and a high-κ dielectric for ultrafast graphene-based electro-absorption modulators

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hitesh Agarwal ◽  
Bernat Terrés ◽  
Lorenzo Orsini ◽  
Alberto Montanaro ◽  
Vito Sorianello ◽  
...  
Keyword(s):  
Boron Nitride ◽  
Hafnium Oxide ◽  
High Speed ◽  
Hexagonal Boron Nitride ◽  
Temperature Stability ◽  
Cost Effective ◽  
Fold Increase ◽  
Building Blocks ◽  
High Quality ◽  
New Device

AbstractElectro-absorption (EA) waveguide-coupled modulators are essential building blocks for on-chip optical communications. Compared to state-of-the-art silicon (Si) devices, graphene-based EA modulators promise smaller footprints, larger temperature stability, cost-effective integration and high speeds. However, combining high speed and large modulation efficiencies in a single graphene-based device has remained elusive so far. In this work, we overcome this fundamental trade-off by demonstrating the 2D-3D dielectric integration in a high-quality encapsulated graphene device. We integrated hafnium oxide (HfO2) and two-dimensional hexagonal boron nitride (hBN) within the insulating section of a double-layer (DL) graphene EA modulator. This combination of materials allows for a high-quality modulator device with high performances: a ~39 GHz bandwidth (BW) with a three-fold increase in modulation efficiency compared to previously reported high-speed modulators. This 2D-3D dielectric integration paves the way to a plethora of electronic and opto-electronic devices with enhanced performance and stability, while expanding the freedom for new device designs.

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