Marnix van der Kolk

O-Demethylation (ODM) is a strategic tool to unlock lignin applications for drop-in and new commodity, fine & specialty chemicals.

Abstract

Lignin represents the largest aromatic carbon resource in plants, holding significant promise as a renewable feedstock for bioaromatics and other cyclic hydrocarbons in the context of the circular bioeconomy. However, the methoxy groups of aryl methyl ethers, abundantly found in technical lignins and lignin-derived chemicals, limit their pertinent chemical reactivity and broader applicability. Unlocking the phenolic hydroxyl functionality through O-demethylation (ODM) has emerged as a valuable approach to mitigate this need and enables further applications. In this review, we provide a comprehensive summary of the progress in the valorization of technical lignin and lignin-derived chemicals via ODM, both catalytic and non-catalytic reactions. Furthermore, a detailed analysis of the properties and potential applications of the O-demethylated products is presented, accompanied by a systematic overview of available ODM reactions. This review primarily focuses on enhancing the phenolic hydroxyl content in lignin-derived species through ODM, showcasing its potential in the catalytic funneling of lignin and value-added applications. A comprehensive synopsis and future outlook are included in the concluding section of this review.

Anxiety disorders significantly impact daily lives. Patients suffering from anxiety sometimes show low testosterone in their blood and can benefit from testosterone treatment. Our recent article discovered the link between low testosterone, anxiety, and the role of TACR3.

In our paper, we show how severity of alcohol relapse in rats can affect psilocybin’s mode of action

Nature, Published online: 20 December 2023; doi:10.1038/s41586-023-06792-0

Coscientist is an artificial intelligence system driven by GPT-4 that autonomously designs, plans and performs experiments by incorporating large language models empowered by tools such as internet and documentation search, code execution and experimental automation.

We present a novel, greener chloromethylation procedure for organosolv aspen lignin under mild reaction conditions without Lewis acid as a catalyst and in acetic acid as a solvent. This synthetic protocol provides a reliable approach to chloromethylated lignin (CML) and means to obtain valuable lignin derivatives The resulted CML was subsequently transformed into 1-methylimidazolium lignin (ImL), which effectively serves as a stabilizing agent for Pd/CuO nanoparticles (Pd/CuO-NPs). To evaluate the versatility of developed lignin-based catalyst, we investigate its performance in a series of carbon-carbon bond formation reactions, including Suzuki-Miyaura, Sonogashira, Heck reactions, and azide-alkyne cycloaddition (click) reaction. Remarkably, this catalyst exhibited a high degree of catalytic efficiency, resulting in reactions with yields ranging from average to excellent. The heterogeneous catalyst demonstrated outstanding recyclability, enabling its reuse for at least 10 consecutive reaction cycles, with yields consistently falling within the range of 42% to 84%. A continuous flow reactor cartridge prototype employing Lignin@Pd/CuO-NPs was developed, yielding results comparable to those achieved in batch reactions. The utilization of Lignin@Pd/CuO-NPs as a catalyst showcases its potential to facilitate diverse carbon-carbon bond formation reactions and underscores its promising recyclability, aligning with the green chemistry metrics and principles of sustainability in chemical processes

Hydrogen borrowing is an attractive and sustainable strategy for carbon-carbon bond formation that enables alcohols to be used as alkylating reagents in place of alkyl halides. However, despite intensive efforts, limited functional group tolerance is observed in this methodology, which we hypothesize is due to the high temperatures and harsh basic conditions often employed. Here we demonstrate that room temperature and functional group tolerant hydrogen borrowing can be achieved with a simple iridium catalyst in the presence of substoichiometric base without an excess of reagents. Achieving high yields necessitates the application of anaerobic conditions to counteract the oxygen sensitivity of the catalytic iridium hydride intermediate, which otherwise leads to catalyst degradation. Substrates containing heteroatoms capable of complexing the catalyst exhibit limited room temperature reactivity, but the application of moderately higher temperatures enables extension to a broad range of medicinally relevant nitrogen rich heterocycles. These newly developed conditions allow alcohols possessing functional groups that were previously incompatible with hydrogen borrowing reactions to be employed

Publication date: 1 February 2024

Source: Catalysis Today, Volume 427

Author(s): M.I. Ávila, M.M. Alonso-Doncel, L. Briones, G. Gómez-Pozuelo, J.M. Escola, D.P. Serrano, A. Peral, J.A. Botas

We describe an approach to stabilize NIR absorbing rhodamine dyes containing phosphinate esters, affording cell permeable photoacoustic probes with maximal absorbance in the range of commercial instrumentation. A derivative of our optimal dye can used for turn-on detection of a disease relevant analyte in living cells and mice.

Abstract

Photoacoustic imaging (PAI) is an emerging imaging technique that uses pulsed laser excitation with near-infrared (NIR) light to elicit local temperature increases through non-radiative relaxation events, ultimately leading to the production of ultrasound waves. The classical xanthene dye scaffold has found numerous applications in fluorescence imaging, however, xanthenes are rarely utilized for PAI since they do not typically display NIR absorbance. Herein, we report the ability of Nebraska Red (NR) xanthene dyes to produce photoacoustic (PA) signal and provide a rational design approach to reduce the hydrolysis rate of ester containing dyes, affording cell permeable probes. To demonstrate the utility of this approach, we construct the first cell permeable rhodamine-based, turn-on PAI imaging probe for hypochlorous acid (HOCl) with maximal absorbance within the range of commercial PA instrumentation. This probe, termed SNR₇₀₀-HOCl, is capable of detecting exogenous HOCl in mice. This work provides a new set of rhodamine-based PAI agents as well as a rational design approach to stabilize esterified versions of NR dyes with desirable properties for PAI. In the long term, the reagents described herein could be utilized to enable non-invasive imaging of HOCl in disease-relevant model systems.

This review emphasizes and comprehensively analyses representative examples of palladium(II)-catalyzed late-stage C−H activation reactions and demonstrates their efficacy in converting C−H bonds at multiple positions within drug (derivative) molecules into diverse functional groups. Specifically, this study elucidates the notable strides made in the realm of late-stage C−H activation of drug (derivatives) molecules employing Pd (II) catalysts.

Abstract

This review comprehensively analyses representative examples of Pd(II)-catalyzed late-stage C−H activation reactions and demonstrates their efficacy in converting C−H bonds at multiple positions within drug (derivative) molecules into diverse functional groups. These transformative reactions hold immense potential in medicinal chemistry, enabling the efficient and selective functionalization of specific sites within drug molecules, thereby enhancing their pharmacological activity and expanding the scope of potential drug candidates. Although notable articles have focused on late-stage C−H functionalization reactions of drug-like molecules using transition-metal catalysts, reviews specifically focusing on late-stage C−H functionalization reactions of drug (derivative) molecules using Pd(II) catalysts are required owing to their prominence as the most widely utilized metal catalysts for C−H activation and their ability to introduce a myriad of functional groups at specific C−H bonds. The utilization of Pd-catalyzed C−H activation methodologies demonstrates impressive success in introducing various functional groups, such as cyano (CN), fluorine (F), chlorine (Cl), aromatic rings, olefin, alkyl, alkyne, and hydroxyl groups, to drug (derivative) molecules with high regioselectivity and functional-group tolerance. These breakthroughs in late-stage C−H activation reactions serve as invaluable tools for drug discovery and development, thereby offering strategic options to optimize drug candidates and drive the exploration of innovative therapeutic solutions.

The dynamic response of single atom catalysts to a reactive environment is an increasingly significant topic for understanding the reaction mechanism at the molecular level. In particular, single atoms may experience dynamic aggregation into clusters or nanoparticles driven by thermodynamic and kinetic factors. Herein, we will uncover the inherent mechanistic nuances that determine the dynamic profile during the reaction, including the intrinsic stability and site-migration barrier of single atoms, external stimuli (temperature, voltage, and adsorbates), and the influence of catalyst support. Such dynamic aggregation can have beneficial or deleterious effects on the catalytic performance depending on the optimal initial state. We will highlight those examples where in situ formed clusters, rather than single atoms, serve as catalytically active sites for improved catalytic performance. This is followed by the introduction of typical operando techniques to understand the structural evolution. Finally, we will briefly discuss the emerging strategies via confinement and defect-engineering to regulate dynamic aggregation.

9-Azahomocubane is unique amongst the nitrogen derivatives of homocubane, as it contains a secondary nitrogen atom, which can be used as a building block through amide bond formation. Herein reported is the first synthesis of 9-azahomocubane, which was achieved via a rarely utilized Stieglitz rearrangement, and confirmed by X-ray crystal structure analysis. The chemical stability of 9-azahomocubane exceeds that of the 1-azahomocubane, as predicted, although the basicity and calculated strain energy are similar.

Abstract

Homocubane, a highly strained cage hydrocarbon, contains two very different positions for the introduction of a nitrogen atom into the skeleton, e. g., a position 1 exchange results in a tertiary amine whereas position 9 yields a secondary amine. Herein reported is the synthesis of 9-azahomocubane along with associated structural characterization, physical property analysis and chemical reactivity. Not only is 9-azahomocubane readily synthesized, and found to be stable as predicted, the basicity of the secondary amine was observed to be significantly lower than the structurally related azabicyclo[2.2.1]heptane, although similar to 1-azahomocubane.