Deprotometalation-iodolysis and computed CH acidity of 1,2,3- and 1,2,4-triazoles. Application to the synthesis of resveratrol analogues

International audience1-Aryl- and 2-aryl-1,2,3-triazoles were synthesized by N-arylation of the corresponding azoles using aryl iodides. The deprotometalations of 1-phenyl-1,2,3-triazole and -1,2,4-triazole were performed using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination and occurred at the most acidic site, affording by iodolysis the 5-substituted derivatives. Dideprotonation was noted from 1-(2-thienyl)-1,2,4-triazole by increasing the amount of base. From 2-phenyl-1,2,3-triazoles, and in particular from 2-(4-trifluoromethoxy)phenyl-1,2,3-triazole, reactions at the 4 position of the triazolyl, but also ortho to the triazolyl on the phenyl group, were observed. The results were analyzed with the help of the CH acidities of the substrates, determined in THF solution using the DFT B3LYP method. 4-Iodo-2-phenyl-1,2,3-triazole and 4-iodo-2-(2-iodophenyl)-1,2,3-triazole were next involved in Suzuki coupling reactions to furnish the corresponding 4-arylated and 4,2’-diarylated derivatives. When evaluated for biological activities, the latter (which are resveratrol analogues) showed moderate antibacterial activity and promising antiproliferative effect against MDA-MB-231 cell line

Advances on antiviral activity of Morus spp. plant extracts: Human coronavirus and virus-related respiratory tract infections in the spotlight

(1) Background: Viral respiratory infections cause life-threatening diseases in millions of people worldwide every year. Human coronavirus and several picornaviruses are responsible for worldwide epidemic outbreaks, thus representing a heavy burden to their hosts. In the absence of specific treatments for human viral infections, natural products offer an alternative in terms of innovative drug therapies. (2) Methods: We analyzed the antiviral properties of the leaves and stem bark of the mulberry tree (Morus spp.). We compared the antiviral activity of Morus spp. on enveloped and nonenveloped viral pathogens, such as human coronavirus (HCoV 229E) and different members of the Picornaviridae family—human poliovirus 1, human parechovirus 1 and 3, and human echovirus 11. The antiviral activity of 12 water and water–alcohol plant extracts of the leaves and stem bark of three different species of mulberry—Morus alba var. alba, Morus alba var. rosa, and Morus rubra—were evaluated. We also evaluated the antiviral activities of kuwanon G against HCoV-229E. (3) Results: Our results showed that several extracts reduced the viral titer and cytopathogenic effects (CPE). Leaves’ water-alcohol extracts exhibited maximum antiviral activity on human coronavirus, while stem bark and leaves’ water and water-alcohol extracts were the most effective on picornaviruses. (4) Conclusions: The analysis of the antiviral activities of Morus spp. offer promising applications in antiviral strategies

Fractionation: an essential tool for lignin valorization

Lignin is a hydrophobic three-dimensional polymer that acts as a binder accounting for the plants structural integrity and as a regulator for the water flux inside the cell wall. Lignin utilization as a potential feedstock for chemical products has attracted more and more attention. Being one of the three main constituents in biomass, it represents a very attractive low-cost, renewable and largely available starting material. However, lignin is difficult to decompose due to its structural complexity and its high stability and up to now most of lignin is burned as a source of energy. Nowadays valorization of lignin and its transformation into small high value chemicals represent a real challenge and is fully linked to the complexity and the heterogeneity of the starting material. Such variability originates from the source of the biomass, the growing parameters and the extraction conditions. One of the best ways to degrade lignin is by using oxidative depolymerization processes. The main drawback of these methods is the possibility of a fast recombination of the small molecules which are already part of the raw material performed by oxygen-based radical species [1]. In order to obtain more homogeneous starting material for the following oxidative treatments, we set-up an industrial fractionation method. The starting material which has been used in this work has been the Lignin ProtobindTM1000 which is an agricultural fiber soda pulp. The fractionation step is a necessary tool to obtain different fractions which appear much more consistent in terms of average molecular weight, polydispersity and solubility. In this work ProtobindTM1000 has been dissolved in an aqueous/ethanol solution and submitted firstly to a microfiltration under vacuum in order to eliminate the insoluble residue. Then it undergoes the cross-flow filtration process using two subsequent membranes with a cut-off of 3 kDa and 1 kDa. All the retentate and permeate fractions of the fractionation process have been fully characterized in terms of composition, chemical and physical properties. This strategy has offered an essential tool for a more efficient lignin valorization allowing to identify specific applications for all the different fractions, spanning from the material science [2] to the preparative organic chemistry. Acknowledgements This work has been performed as part of the ValorPlus Project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no FP7-KBBE-2013-7-613802

Chemical Composition, Antibacterial Activity using Micro-broth Dilution Method and Antioxidant Activity of Essential Oil and Water Extract from Aerial Part of Tunisian Thymus algeriensis Boiss. & Reut.

In this study, we investigated the chemical composition, antioxidant and antibacterial activities of essential oil and aqueous extract from Thymus algeriensis Boiss. & Reut growing in Tunisia. GC/MS analysis of essential oil from the aerial part of the plant led to identifying 54 constituents representing 96.87 % of the total oil composition. Monoterpenes represented the major components of the essential oil. On the other hand, the aqueous extract and the essential oil were screened for their antioxidant and antibacterial activities. The latter was assessed against Gram-negative and Gram-positive bacterial strains using the broth dilution micro method for the determination of antibacterial activity. The antioxidant activity was evaluated using the DPPH scavenging activity and Ferric Reducing/Antioxidant Power (FRAP) assays. The essential oil was found to be more active in antibacterial screening (MIC = 0.54 μg/mL). Whereas the aqueous extract exhibited the most potent antioxidant activity with (IC50 = 0.04 μg/mL). UHPLC ESI(-)-HRMS/MS analysis of the aqueous extract allowed tentative identification of its constituents and showed that it is rich in phenolic compounds. Luteolin-glucuronide was found to be the most abundant compound followed by Vicenin-2 and Apigenin-diglucuronide. © 2022 Har Krishan Bhalla & Sons

Photocatalytic pre-treatment for lignin enzymatic depolymerization

Homogeneous lignin fractions coming from industrial ultrafiltration processes were subjected to a photocatalytic oxidation process in order to reduce their molecular weight and produce more accessible substrates for the following enzymatic treatment. Early results indicate that due to the effectiveness of the photocatalytic step which accounts for a reduction of the mean molecular weight of treated lignins, the enzymatic production of small degradation compounds is favoured. 1. Scope The oxidation of lignin for the production of valuable chemicals is an interesting application of photocatalysis, particularly as integrated process with other oxidation technologies.1 In the present work the photocatalytic oxidation of lignin is studied as a pre-process for enzymatic depolymerization, in order to reduce the average molecular weight and enhance the performance of the enzymatic degradation. 2. Results and discussion In this work raw lignin has been physically separated by industrial sequential ultrafiltrations on different membranes in order to obtain more homogeneous starting materials for the following degradation processes. The photocatalytic oxidation of lignin was performed in aqueous basic solution using nanocrystalline ZnO supported on glass and UV-A radiation. After 28 h of photocatalytic treatment in a batch reactor lignin results partially degraded (UV spectroscopy, A365 decreased by 25%) and GPC analyses indicate a reduction of both the number-average molecular weight (Mn decreased by >20%) and the polydispersity index (PDI decreased by >30%). Early results on the enzymatic digestion of the partially degraded lignin indicate an enhanced production of small degradation compounds. 3. Conclusions These early results indicate that the photocatalytic process can be an interesting pre-treatment for lignin degradation. The assessment of the two consecutive processes, exploiting the high activity of the photocatalytic oxidation combined to the selectivity of the enzymatic treatment, will pave the way to the development of a fully integrated approach for new lignin valorization processes. Acknowledgements This work has been performed as part of the ValorPlus Project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no FP7-KBBE-2013-7- 613802. References 1. Shao-Hai Li, Siqi Liu, Juan Carlos Colmenares, Yi-Jun Xu, Green Chem. 2016, 18, 594-60

Fractionation: an essential tool for lignin valorization

Lignin is a hydrophobic three-dimensional polymer that acts as a binder accounting for the plants structural integrity and as a regulator for the water flux inside the cell wall. Lignin utilization as a potential feedstock for chemical products has attracted more and more attention. Being one of the three main constituents in biomass, it represents a very attractive low-cost, renewable and largely available starting material. However, lignin is difficult to decompose due to its structural complexity and its high stability and up to now most of lignin is burned as a source of energy. Nowadays valorization of lignin and its transformation into small high value chemicals represent a real challenge and is fully linked to the complexity and the heterogeneity of the starting material. Such variability originates from the source of the biomass, the growing parameters and the extraction conditions. One of the best ways to degrade lignin is by using oxidative depolymerization processes. The main drawback of these methods is the possibility of a fast recombination of the small molecules which are already part of the raw material performed by oxygen-based radical species [1]. In order to obtain more homogeneous starting material for the following oxidative treatments, we set-up an industrial fractionation method. The starting material which has been used in this work has been the Lignin ProtobindTM1000 which is an agricultural fiber soda pulp. The fractionation step is a necessary tool to obtain different fractions which appear much more consistent in terms of average molecular weight, polydispersity and solubility. In this work ProtobindTM1000 has been dissolved in an aqueous/ethanol solution and submitted firstly to a microfiltration under vacuum in order to eliminate the insoluble residue. Then it undergoes the cross-flow filtration process using two subsequent membranes with a cut-off of 3 kDa and 1 kDa. All the retentate and permeate fractions of the fractionation process have been fully characterized in terms of composition, chemical and physical properties. This strategy has offered an essential tool for a more efficient lignin valorization allowing to identify specific applications for all the different fractions, spanning from the material science [2] to the preparative organic chemistry. Acknowledgements This work has been performed as part of the ValorPlus Project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no FP7-KBBE-2013-7-613802

Chemo-enzymatic depolymerization of lignin

Lignin is a highly complex phenolic matrix that acts as a binder in plants conferring them structural integrity and strength, and is one of the three major subcomponents of lignocellulosic biomass. Although burning lignin is still considered a valuable contribution in saving fossil sources, the exploitation of this extremely abundant natural polymer in terms of higher value-added applications is very appealing as it represents the only viable source to produce aromatic compounds as fossil fuels alternative. Due to the very broad composition in terms of molecular weight of the raw material, a pretreatment strategy becomes necessary for an efficient lignin valorization as macromolecular building block for polymeric materials or as precursor for aromatic small molecules. This procedure is an essential tool for a thorough exploitation of the main three different fractions recovered, namely a high, an intermediate and a low molecular weight fraction. The first one is characterized by the presence of high molecular weight polymers and is used without further chemical modification for developing bio-based polymeric materials;[1] the last one can be separated by chromatography into small aromatic molecules for preparative organic chemistry; whereas the middle fraction, characterized by an intermediate molecular weight, is the ideal starting material for oxidative depolymerization assays.[2,3] On this fraction, a new cascade process has been investigated involving at first a chemical step aiming at a partial conversion of macromolecules to lower molecular weight intermediates followed by a biocatalytic step performed by different classes of O2-dependent laccases (EC 1.10.3.2) in the presence of TEMPO as a mediator. Promising results have been obtained and extensive research is now in progress