Mechanochemical difluoromethylations of ketones.

We present a mechanochemical synthesis of difluoromethyl enol ethers. Utilizing an in situ generation of difluorocarbenes, ketones are efficiently converted to the target products under solvent-free conditions. The reactions proceed at room temperature and are complete within 90 minutes, demonstrating both efficiency and experimental simplicity.

Mechanochemical Conditions for Intramolecular N-O Couplings via Rhodium Nitrenoids Generated from N-Acyl Sulfonimidamides.

Starting from N-acyl sulfonimidamides, mechanochemically generated rhodium nitrenoids undergo intramolecular N-O couplings to provide unprecedented 1,3,2,4-oxathiadiazole 3-oxides in good to excellent yields. The cyclization proceeds efficiently with a catalyst loading of only 0.5 mol % in the presence of phenyliodine(III) diacetate (PIDA) as oxidant.

Cyclic Sulfoximines as Methyl and Perdeuteromethyl Transfer Agents and Their Applications in Photoredox Catalysis.

Benzo[1,3,2]dithiazole-1,1,3-trioxides are bench-stable and easy-to-use reagents. In photoredox catalysis, they generate methyl and perdeuteromethyl radicals which can add to a variety of radical acceptors, including olefins, acrylamides, quinoxalinones, isocyanides, enol silanes, and N-Ts acrylamide. As byproduct, a salt is formed which can be regenerated to the original methylating agent.

Molecular Recognition in Mechanochemistry: Insights from Solid-State NMR Spectroscopy.

Molecular-recognition events are highly relevant in biology and chemistry. In the present study, we investigated such processes in the solid state under mechanochemical conditions using the formation of racemic phases upon reacting enantiopure entities as example. As test systems, α-(trifluoromethyl)lactic acid (TFLA) and the amino acids serine and alanine were used.

Syntheses of Sulfilimines by Iron-Catalyzed Iminations of Sulfides with 2,2,2-Trichloroethyl Sulfamate.

N-protected sulfilimines are prepared by imination of sulfides with a combination of 2,2,2-trichloroethyl sulfamate (HNTces), (diacetoxyiodo)benzene (PIDA), and a catalytic amount of iron triflate. The reaction proceeds at room temperature, and after only 3 h a wide range of acyclic and cyclic Tces-sulfilimines with various functional groups and (hetero)aryl substituents can be obtained. By subsequent oxidation followed by deprotection, the products are converted into H-sulfoximines.

Synthesis of Benzo[][1,4,3]oxathiazin-3-one 1-Oxides from H--(2-Hydroxyaryl)sulfoximines.

Cyclizations of H--(2-hydroxyaryl)sulfoximines with 1,1'-carbonyldiimidazol (CDI) give unprecedented benzo[][1,4,3]oxathiazin-3-one 1-oxides in good yields. The standard synthetic protocol involves the use of DCE at an increased temperature for 16 h. Under mechanochemical conditions, a representative product was obtained without a solvent at ambient temperature in only 60 min.

Azasulfur(iv) derivatives of sulfite and sulfinate esters by formal S-S bond insertion of dichloramines.

Azasulfur(vi) compounds such as sulfoximines and sulfonimidamides are attractive due to the unique properties of the S[double bond, length as m-dash]N bond. While the synthesis of these carbon-attached sulfonimidoyl derivatives is well-established, the situation is different for their heteroatom-bound counterparts. In this work, we propose azasulfur(iv) esters as platform chemicals that can be derivatized to obtain all types of S[double bond, length as m-dash]N functional groups, among these are the poorly accessible, all-heteroatom imidosulfate esters.

Microbially conjugated bile salts found in human bile activate the bile salt receptors TGR5 and FXR.

Background: Bile salts of hepatic and microbial origin mediate interorgan cross talk in the gut-liver axis. Here, we assessed whether the newly discovered class of microbial bile salt conjugates (MBSCs) activate the main host bile salt receptors (Takeda G protein-coupled receptor 5 [TGR5] and farnesoid X receptor [FXR]) and enter the human systemic and enterohepatic circulation.

Methods: N-amidates of (chenodeoxy) cholic acid and leucine, tyrosine, and phenylalanine were synthesized.

Rhodium(II)-Catalyzed N-H Insertions of Carbenes under Mechanochemical Conditions.

Under mechanochemical conditions in a mixer mill, Rh(OAc) catalyzes the reaction between aryldiazoesters and anilines to give α-amino esters. The process proceeds under mild conditions and is insensitive to air. It is solvent-free and scalable.

Mechanochemical Iron-Catalyzed Nitrene Transfer Reactions: Direct Synthesis of N-Acyl Sulfonimidamides from Sulfinamides and Dioxazolones.

A mechanochemical synthesis of sulfonimidamides by iron(II)-catalyzed exogenous ligand-free N-acyl nitrene transfer to sulfinamides is reported. The one-step method tolerates a wide range of sulfinamides with various substituents under solvent-free ambient conditions. Compared to its solution-phase counterpart, this mechanochemical approach shows better conversion and chemoselectivity.

Unexpected Single-Ligand Occupancy and Negative Cooperativity in the SARS-CoV-2 Main Protease.

Many homodimeric enzymes tune their functions by exploiting either negative or positive cooperativity between subunits. In the SARS-CoV-2 Main protease (Mpro) homodimer, the latter has been suggested by symmetry in most of the 500 reported protease/ligand complex structures solved by macromolecular crystallography (MX). Here we apply the latter to both covalent and noncovalent ligands in complex with Mpro.

The effect of methyl group rotation on H-H solid-state NMR spin-diffusion spectra.

Fast magic-angle spinning (MAS) NMR experiments open the way for proton-detected NMR studies and have been explored in the past years for a broad range of materials, comprising biomolecules and pharmaceuticals. Proton-spin diffusion (SD) is a versatile polarization-transfer mechanism and plays an important role in resonance assignment and structure determination. Recently, the occurrence of negative cross peaks in 2D H-H SD-based spectra has been reported and explained with higher-order SD effects, in which the chemical shifts of the involved quadruple of nuclei need to compensate each other.

Opportunities and Challenges in Applying Solid-State NMR Spectroscopy in Organic Mechanochemistry.

In recent years it is shown that mechanochemical strategies can be beneficial in directed conversions of organic compounds. Finding new reactions proved difficult, and due to the lack of mechanistic understanding of mechanochemical reaction events, respective efforts have mostly remained empirical. Spectroscopic techniques are crucial in shedding light on these questions.

Mechanochemical Oxidative Degradation of Thienopyridine Containing Drugs: Toward a Simple Tool for the Prediction of Drug Stability.

The long-term stability of an active-pharmaceutical ingredient and its drug products plays an important role in the licensing process of new pharmaceuticals and for the application of the drug at the patient. It is, however, difficult to predict degradation profiles at early stages of the development of new drugs, making the entire process very time-consuming and costly. Forced mechanochemical degradation under controlled conditions can be used to realistically model long-term degradation processes naturally occurring in drug products, avoiding the use of solvents, thus excluding irrelevant solution-based degradation pathways.

Mechanochemical Synthesis of Stimuli Responsive Microgels.

Mechanochemical approaches are widely used for the efficient, solvent-free synthesis of organic molecules, however their applicability to the synthesis of functional polymers has remained underexplored. Herein, we demonstrate for the first time that mechanochemically triggered free-radical polymerization allows solvent- and initiator-free syntheses of structurally and morphologically well-defined complex functional macromolecular architectures, namely stimuliresponsive microgels. The developed mechanochemical polymerization approach is applicable to a variety of monomers and allows synthesizing microgels with tunable chemical structure, variable size, controlled number of crosslinks and reactive functional end-groups.

Correction: Sankaranarayanan et al. Auger Emitter Conjugated PARP Inhibitor for Therapy in Triple Negative Breast Cancers: A Comparative In-Vitro Study. 2022, , 230.

The authors wish to replace the 'Author Contributions' statement and the affiliation for Jochen Maurer of this article [...

Synthesis of N-Monosubstituted Sulfondiimines by Metal-free Iminations of Sulfilimium Salts.

Sulfondiimines are marginalized entities among nitrogen-containing organosulfur compounds, despite offering promising properties for applications in various fields including medicinal and agrochemical. Herein, we present a metal-free and rapid synthetic procedure for the synthesis of N-monosubstituted sulfondiimines that overcomes current limitations in their synthetic accessibility. Particularly, S,S-dialkyl substrates, which are commonly difficult to convert by existing methods, react well with a combination of iodine, 1,8-diazabicyclo[5.

A One-Pot Domino Reaction Providing Fluorinated 5,6-Dihydro-1,2-thiazine 1-Oxides from Sulfoximines and 1-Trifluoromethylstyrenes.

-Trifluoroacetylated (-TFA) sulfoximines react with 1-trifluoromethylstyrenes in a one-pot domino reaction to give fluorinated 5,6-dihydro-1,2-thiazine 1-oxides in good to high yields. The process involves three sequential reaction steps that can be characterized as (1) nucleophilic allylic substitution (S2'), (2) hydrolysis, and (3) intramolecular nucleophilic vinylic substitution (SV). The products can further be modified by defluorination.

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr/PPh and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior.

Cholesterol reacts under Appel conditions (CBr/PPh) to give 3,5-cholestadiene (elimination) and 3β-bromocholest-5-ene (substitution with retention of configuration). Thus, the bromination of cholesterol deviates from the stereochemistry of the standard Appel mechanism due to participation of the Δ π-electrons. In contrast, the subsequent azidolysis (NaN/DMF) of 3β-bromocholest-5-ene proceeds predominantly by Walden inversion (S2) affording 3α-azidocholest-5-ene.

Synthesis of -Sulfinylanilines from -Alkyl Sulfoximines and Arynes.

-Alkyl sulfoximines react with arynes generated under mild conditions providing -sulfinylanilines in good yields. The transformation is characterized by a broad substrate scope and a good functional group tolerance. The structure of a reaction product was confirmed by single-crystal X-ray diffraction.

Reshuffle Bonds by Ball Milling: A Mechanochemical Protocol for Charge-Accelerated Aza-Claisen Rearrangements.

This study presents the development of a mechanochemical protocol for a charge-accelerated aza-Claisen rearrangement. The protocol waives the use of commonly applied transition metals, ligands, or pyrophoric Lewis acids, e.g.

Evaluation of Chiral Organosulfur Compounds on Their Activity against the Malaria Parasite .

Malaria is one of the deadliest tropical diseases, especially causing havoc in children under the age of five in Africa. Although the disease is treatable, the rapid development of drug resistant parasites against frontline drugs requires the search for novel antimalarials. In this study, we tested a series of organosulfur compounds from our internal library for their antiplasmodial effect against asexual and sexual blood stages.