A scalable carboxylation route to furan-2,5-dicarboxylic acid Dick, Graham R; Frankhouser, Amy D; Banerjee, Aanindeeta ...
Green chemistry : an international journal and green chemistry resource : GC,
2017, Letnik:
19, Številka:
13
Journal Article
Recenzirano
Furan-2,5-dicarboxylic acid (FDCA) is a biomass-derived diacid that can be used to make polymers including polyethylene furandicarboxylate (PEF), a highly attractive substitute for petroleum-derived ...polyethylene terephthalate (PET). Current FDCA syntheses require edible fructose as the feedstock, entail a difficult oxidation step that generates undesirable aldehyde impurities, and have moderate yields. As an alternative, carbonate-promoted C-H carboxylation enables the synthesis of FDCA from 2-furoic acid and CO2. This route is potentially advantageous because 2-furoic acid is made from furfural, a feedstock produced commercially from inedible lignocellulosic biomass, and it obviates late-stage oxidation. In the carboxylation reaction, salt mixtures composed of alkali furan-2-carboxylate (furoate) and alkali carbonate (M2CO3) are heated under CO2 in the absence of solvent or catalysts to form furan-2,5-dicarboxylate (FDCA2-), which is subsequently protonated to produce FDCA. Previously, high yields were achieved on small-scale reactions using caesium furoate and Cs2CO3. In this work, we investigate the carboxylation reaction using alkali furoate/M2CO3 salts containing cation blends and describe reaction conditions that provide high yields on a preparative scale. We show that the carboxylation proceeds efficiently with K+/Cs+ blends that have a high K+ content (up to 4 : 1 K+ : Cs+). Removing H2O, which is a by-product of the reaction, is important for suppressing decomposition pathways. The accumulation of the FDCA2- product inhibits the reaction. Integrating these lessons, we demonstrate the carboxylation of furoate on a 1 mol scale using a fixed-bed flow reactor with 89% isolated yield of pure FDCA upon protonation.
Changes in the enzymatic activity of protein arginine methyltransferase (PRMT) 5 have been associated with cancer; however, the protein's role in acute myeloid leukemia (AML) has not been fully ...evaluated. Here, we show that increased PRMT5 activity enhanced AML growth in vitro and in vivo while PRMT5 downregulation reduced it. In AML cells, PRMT5 interacted with Sp1 in a transcription repressor complex and silenced miR-29b preferentially via dimethylation of histone 4 arginine residue H4R3. As Sp1 is also a bona fide target of miR-29b, the miR silencing resulted in increased Sp1. This event in turn led to transcription activation of FLT3, a gene that encodes a receptor tyrosine kinase. Inhibition of PRMT5 via sh/siRNA or a first-in-class small-molecule inhibitor (HLCL-61) resulted in significantly increased expression of miR-29b and consequent suppression of Sp1 and FLT3 in AML cells. As a result, significant antileukemic activity was achieved. Collectively, our data support a novel leukemogenic mechanism in AML where PRMT5 mediates both silencing and transcription of genes that participate in a 'yin-yang' functional network supporting leukemia growth. As FLT3 is often mutated in AML and pharmacologic inhibition of PRMT5 appears feasible, the PRMT5-miR-29b-FLT3 network should be further explored as a novel therapeutic target for AML.
Solvent-free chemistry has been used to streamline synthesis, reduce waste, and access novel reactivity, but the physical nature of the reaction medium in the absence of solvent is often poorly ...understood. Here we reveal the phase behavior that enables the solvent-free carboxylation reaction in which carbonate, furan-2-carboxylate (furoate), and CO2 react to form furan-2,5-dicarboxylate (FDCA2–). This transformation has no solution-phase analogue and can be applied to convert lignocellulose into performance-advantaged plastics. Using operando powder X-ray diffraction and thermal analysis to elucidate the temperature- and conversion-dependent phase composition, we find that the reaction medium is a heterogeneous mixture of a ternary eutectic molten phase, solid Cs2CO3, and solid Cs2FDCA. During the reaction, the amounts of molten phase and solid Cs2CO3 diminish as solid Cs2FDCA accumulates. These insights are critical for increasing the scale of furoate carboxylation and provide a framework for guiding the development of other solvent-free transformations.
The ability to functionalize hydrocarbons with CO2 could create opportunities for high-volume CO2 utilization. However, current methods to form carbon–carbon bonds between hydrocarbons and CO2 ...require stoichiometric consumption of very resource-intensive reagents to overcome the low reactivity of these substrates. Here, we report a simple semi-continuous cycle that converts aromatic hydrocarbons, CO2 and alcohol into aromatic esters without consumption of stoichiometric reagents. Our strategy centres on the use of solid bases composed of an alkali carbonate (M2CO3, where M+ = K+ or Cs+) dispersed over a mesoporous support. Nanoscale confinement disrupts the crystallinity of M2CO3 and engenders strong base reactivity at intermediate temperatures. The overall cycle involves two distinct steps: (1) CO32–-promoted C–H carboxylation, in which the hydrocarbon substrate is deprotonated by the supported M2CO3 and reacts with CO2 to form a supported carboxylate (RCO2M); and (2) methylation, in which RCO2M reacts with methanol and CO2 to form an isolable methyl ester with concomitant regeneration of M2CO3.
DNMT3B encodes a DNA methyltransferase implicated in aberrant epigenetic changes contributing to leukemogenesis. We tested whether DNMT3B expression, measured by NanoString nCounter assay, associates ...with outcome, gene and microRNA expression and DNA methylation profiles in 210 older (⩾60 years) adults with primary, cytogenetically normal acute myeloid leukemia (CN-AML). Patients were dichotomized into high versus low expressers using median cut. Outcomes were assessed in the context of known CN-AML prognosticators. Gene and microRNA expression, and DNA methylation profiles were analyzed using microarrays and MethylCap-sequencing, respectively. High DNMT3B expressers had fewer complete remissions (CR; P=0.002) and shorter disease-free (DFS; P=0.02) and overall (OS; P<0.001) survival. In multivariable analyses, high DNMT3B expression remained an independent predictor of lower CR rates (P=0.04) and shorter DFS (P=0.04) and OS (P=0.001). High DNMT3B expression associated with a gene expression profile comprising 363 genes involved in differentiation, proliferation and survival pathways, but with only four differentially expressed microRNAs (miR-133b, miR-148a, miR-122, miR-409-3p) and no differential DNA methylation regions. We conclude that high DNMT3B expression independently associates with adverse outcome in older CN-AML patients. Gene expression analyses suggest that DNMT3B is involved in the modulation of several genes, although the regulatory mechanisms remain to be investigated to devise therapeutic approaches specific for these patients.
Carbon-neutral liquid fuel generation is essential for decarbonizing sectors that cannot readily electrify. Recently commercialized acetogenic gas fermentation offers an alternative to conventional ...biofuels that circumvents efficiency limitations and land requirements, provided the requisite H2/CO feedstocks can be generated efficiently using renewable inputs. CO2 electrolysis is under development for this application but suffers from scalability challenges and impurity sensitivity. We describe an alternative that utilizes dispersed alkali carbonates as reverse water-gas shift (RWGS) catalysts to convert H2 and CO2 to an appropriate ratio of CO/CO2/H2 for acetogenic fermentation. Using a fixed-bed reactor operating at industrially relevant space velocity, we demonstrate equilibrium RWGS conversion starting at 430°C that remains stable over days, even with 50 ppm H2S. The combination of carbonate-catalyzed RWGS, water electrolysis, and gas fermentation could convert electricity to ethanol with nearly 50% energy efficiency (higher heating value), providing a compelling option for renewable liquid fuel production.
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•Dispersed alkali carbonates are highly active low-temperature RWGS catalysts•Essentially 100% selectivity for CO with no detectable CH4•Multi-day stability with no apparent degradation•Tolerance to 50 ppm H2S impurity in the gas feed
Acetogenic fermentation is a promising technology for liquid fuel generation that currently relies on limited access to CO-rich industrial exhaust. Li et al. report highly active, selective, and robust reverse water-gas shift catalysts based on alkali carbonates that can produce gas fermentation feedstocks from CO2 and H2 at moderate temperatures.
Furan-2,5-dicarboxylic acid (FDCA) is a biomass-derived diacid that can be used to make polymers including polyethylene furandicarboxylate (PEF), a highly attractive substitute for petroleum-derived ...polyethylene terephthalate (PET). Current FDCA syntheses require edible fructose as the feedstock, entail a difficult oxidation step that generates undesirable aldehyde impurities, and have moderate yields. As an alternative, carbonate-promoted C-H carboxylation enables the synthesis of FDCA from 2-furoic acid and CO
2
. This route is potentially advantageous because 2-furoic acid is made from furfural, a feedstock produced commercially from inedible lignocellulosic biomass, and it obviates late-stage oxidation. In the carboxylation reaction, salt mixtures composed of alkali furan-2-carboxylate (furoate) and alkali carbonate (M
2
CO
3
) are heated under CO
2
in the absence of solvent or catalysts to form furan-2,5-dicarboxylate (FDCA
2−
), which is subsequently protonated to produce FDCA. Previously, high yields were achieved on small-scale reactions using caesium furoate and Cs
2
CO
3
. In this work, we investigate the carboxylation reaction using alkali furoate/M
2
CO
3
salts containing cation blends and describe reaction conditions that provide high yields on a preparative scale. We show that the carboxylation proceeds efficiently with K
+
/Cs
+
blends that have a high K
+
content (up to 4 : 1 K
+
: Cs
+
). Removing H
2
O, which is a by-product of the reaction, is important for suppressing decomposition pathways. The accumulation of the FDCA
2−
product inhibits the reaction. Integrating these lessons, we demonstrate the carboxylation of furoate on a 1 mol scale using a fixed-bed flow reactor with 89% isolated yield of pure FDCA upon protonation.
2-Furoic acid is converted to furan-2,5-dicarboxylic acid in high yield on a mole scale using carbonate-promoted C-H carboxylation.
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