Tomas Horsten

Science, Volume 387, Issue 6735, Page 744-749, February 2025.

Molecules that rapidly detoxify nerve agents under physiological conditions might be useful to treat nerve agent poisoning or to support existing treatment strategies. In their Research Article (DOI: 10.1002/chem.202404321), S. Kubik and co-workers show that a sulfonatocalix[4]arene derivative containing two hydroxamic acid residues deactivates highly toxic and persistent V-type nerve agents such as VX with very promising activity. Moreover, the observed increase in activity over the corresponding monosubstituted calixarene appears to be more than just a statistical effect, but also seems to involve additional beneficial effects of the two substituents. This work thus brings supramolecular small-molecule nerve agent scavengers closer to application.

Nature Synthesis, Published online: 22 January 2025; doi:10.1038/s44160-024-00716-0

A general homogeneous hydrogen isotope labelling strategy for unactivated alkyl halides is reported. This approach overcomes the limited selectivity of traditional methods by combining bioinspired carbon–halogen activation and hydrogenation catalysis, enabling the selective and controlled synthesis of deuterium- and tritium-labelled drug molecules, which are crucial for drug discovery.

A borrowing hydrogen approach to produce bio-based surfactants is described. Using amino acids and common alcohols without protecting groups, surfactants are synthesized in one step with a ruthenium catalyst, achieving nearly ideal atom economy, including Gemini surfactants and a quaternary ammonia salt, with remarkable surfactant properties and potential biodegradability, enhancing the broad application profile of these sustainable products.

Abstract

A borrowing hydrogen approach to produce bio-based surfactants is described. The process utilizes ubiquitous amino acids and common alcohols without protecting group manipulations. Surfactants are synthesized in a single step using a commercially available ruthenium-based catalyst in a waste-free manner with nearly ideal atom economy. The versatility of the products is shown by further derivatization resulting in novel Gemini surfactants and a related quaternary ammonia salt. The analysis of selected compounds shows remarkable properties as surfactants. Further studies show their potential biodegradability in nature, which enhances the broad application profile of the sustainable products prepared in this study.

Publication date: 28 February 2025

Source: Tetrahedron Letters, Volume 157

Author(s): Ani Deepthi, C.B. Meenakshy, Devika Krishnan

Nature Communications, Published online: 11 January 2025; doi:10.1038/s41467-025-55912-z

The difluoromethyl group is a crucial fluorinated moiety, and the synthesis of chiral CF₂H-containing analogs is a powerful strategy in drug design and screening. Here, the authors report a strategy for the asymmetric construction of carbon stereocenters featuring a difluoromethyl group via nickel-catalyzed Negishi cross-coupling.

Anti-Markovnikov hydro-functionalization of alkenes is essential for synthesizing natural products, medicinally relevant compounds, and other important molecules. In this context, photocatalysis has emerged as a crucial tool for these reactions. However, existing methods rely on either expensive, or scarce metal photocatalysts, rendering this strategy less feasible for industrial applications. Herein, we disclose the first inexpensive porous heterogeneous material (oxidizing potential: +2.37 V vs SCE) designed to bridge the existing research gap. The careful selection of monomers to prepare the material enables us to achieve hydrocarboxylation, hydroamination, and hydroazidation across a wide range of electron-donating and electron-withdrawing aromatic and aliphatic substrates.

Abstract

Porous materials-based heterogeneous photocatalysts, performing selective organic transformations, are increasing the applicability of photocatalytic reactions due to their ability to merge traditional photocatalysis with structured pores densely decorated with catalytic moiety for efficient mass and charge transfer, as well as added recyclability. We herein disclose a porous crystalline covalent triazine framework (CTF)-based heterogeneous photocatalyst that exhibits excellent photoredox properties for different hydrofunctionalization reactions such as hydrocarboxylations, hydroamination and hydroazidations. The high oxidizing property of this CTF enables the activation of styrenes, followed by regioselective C−N and C−O bond formation at ambient conditions. A change in the physicochemical and optoelectronic properties of the CTF, upon protonation during catalysis, lies at the basis of its photocatalytic properties. This allows us to obtain hydrocarboxylations, hydroamination, and hydroazidations from a myriad of electron-donating and -withdrawing aromatic and aliphatic substrates. This catalytic approach is further extended to late-stage functionalization of bio-active molecules. Finally, detailed characterizations of the CTF and further mechanistic investigations provide mechanistic insights into these reactions.

The electrochemical oxidation of multifunctional catechols represents a “green” and clean alternative pathway to ortho-quinones, which are used to form oligomer networks with branched multi-thiols. In these networks, the catechols are restored and represent adhesive points, which can establish transient interactions with enzymes. These oligomer/enzyme-conjugates are shielding the enzymes from heat stress, thus preventing denaturation.

Abstract

Multifunctional ortho-quinones are required for the formation of thiol-catechol-connectivities (TCC) but can be delicate to handle. We present the electrochemical oxidation of the dipeptide DiDOPA, achieving up to 92 % conversion efficiency of the catechols to ortho-quinones. Graphite and stainless steel could be employed as cost-efficient electrodes. The electrochemical activation yields quinone-solutions, which are free of undesired reactive compounds and eliminates the challenging step of isolating the reactive quinones. The DiDOPA quinones were employed in polyaddition reactions with multi-thiols, forming oligomers that functioned as transient enzyme stabilizers (TES). These TCC-TES-additives improved the thermal stability and the activity of tyrosinase in heat stress assays.

A one-pot multi-component alkene-arene and alkene-alkene aminative coupling reaction has been developed for the synthesis of secondary amines and aziridines. This was achieved through the design, synthesis and implementation of an anomeric amide reagent, capable of promoting catalyst-free alkene chloroamination transformations, installing a formal nitrene precursor that can subsequently undergo either C−H insertion or [2+1] cycloaddition.

Abstract

Despite the prominence of C−N bond forming cross-coupling reactions as a strategy to assemble molecular fragments, aminative coupling approaches, in which two fragments are assembled directly at the heteroatom, represents a rarely exploited retrosynthetic strategy. Herein, we report the design, synthesis, and implementation of an anomeric amide reagent capable of promoting highly regioselective aminative alkene-arene and alkene-alkene coupling reactions. This transformation follows a sequence of catalyst-free chloroamination, N-deprotection, and formal nitrene functionalization, all in one-pot. Due to the simplicity of both the protocol and the building blocks required, high-throughput experimentation (HTE) was employed, in combination with a full-scale scope, to rapidly and efficiently explore a wide range of chemical space and determine the limits of reactivity. In addition, alternative reactivity modes from the functionalized intermediates delivered by this protocol demonstrate the divergent nature of this aminative coupling strategy.

Nature, Published online: 26 November 2024; doi:10.1038/d41586-024-03887-0

We discover a Cold War-era military base beneath the Greenland ice sheet and meet the billion-dollar company building giant quantum computers using light.

Nature, Published online: 27 November 2024; doi:10.1038/d41586-024-03652-3

The earliest known dinosaur fossils are at least 230 million years old, and by 200 million years ago, dinosaurs dominated global ecosystems. Reconstructing food webs using fossil evidence of feeding activity helps to explain this ascendency.