KAT6A and KAT6B genes are two closely related lysine acetyltransferases that transfer an acetyl group from acetyl coenzyme A (AcCoA) to lysine residues of target histone substrates, hence playing a key role in chromatin regulation. KAT6A and KAT6B genes are frequently amplified in various cancer types. In breast cancer, the 8p11-p12 amplicon occurs in 12-15% of cases, resulting in elevated copy numbers and expression levels of chromatin modifiers like KAT6A. Here, we report the discovery of a new acylsulfonamide-benzofuran series as a novel structural class for KAT6A/B inhibition. These compounds were identified through high-throughput screening and subsequently optimized using molecular modeling and cocrystal structure determination. The final tool compound, BAY-184 (29), was successfully validated in an in vivo proof-of-concept study.

Constructing a C-N bond by merging electrochemistry and nickel catalysis is considered a powerful strategy. Herein, we investigate highly efficient intramolecular amination at room temperature with excellent functional group tolerance. Mechanistic studies suggest that the rapid ligand exchange may lead to the Ni-I/Ni-III catalytic cycle. This method not only provides a new perspective for intramolecular amination but also offers a novel approach for constructing the benzothiazole scaffold.

Multinuclear complexes of heavy metals, such as tungsten, have demonstrated considerable potential as candidates for advanced radiocontrast agents. Of particular interest is the development of stable non-ionic compounds with high metal content and reasonably low osmolality in solution. Accordingly, we have synthesized a series of neutral W(V) complexes that contain the W2O2(µ-O)2 core and amino acids or disubstituted EDTA derivatives as ligands. The compounds were prepared from the oxalatotungstate(V) complex via a convenient procedure utilizing microwave heating. Their detailed characterization was accomplished by electrospray ionization high-resolution mass spectrometry (ESI-HRMS), 1H and 13C NMR spectroscopy, elemental analysis, and X-ray crystallography. Further experiments to evaluate the utility of the complexes as radiocontrast media were precluded by their poor aqueous solubility.

Multinuclear tungsten complexes are intriguing candidates for new contrast media that can provide substantial improvements in CT imaging diagnostics. Herein, we present a ligand strategy, based on amino acids, and mono- and disubstituted EDTA derivatives, that enables the development of stable complexes with high tungsten content and reasonably low osmolality. Accordingly, a series of neutral and monoanionic di-μ-sulfido W(V) dimers have been synthesized via a convenient procedure utilizing microwave heating in combination with ion-pair HPLC reaction monitoring. The compounds were characterized in detail by various techniques, including ESI-HRMS, NMR spectroscopy, HPLC, elemental analysis, and X-ray crystallography. The aqueous stability of the complexes under physiologically relevant conditions, and during heat sterilization was also examined as an initial assessment of their potential applicability as radiocontrast agents. Monoanionic complexes featuring monosubstituted EDTA derivatives have demonstrated high stability, while producing a lower number of ions in solution (resulting in lower osmolality) in comparison to their bis-anionic EDTA counterparts. Nevertheless, they exhibited insufficient water solubility for application as intravascular contrast agents. However, our study showed that aqueous solubility of this type of complexes can be tuned by small modifications in the ligand structure.

Electrochemical asymmetric catalysis has emerged as a sustainable and promising approach to the production of chiral compounds and the utilization of both the anode and cathode as working electrodes would provide a unique approach for organic synthesis. However, precise matching of the rate and electric potential of anodic oxidation and cathodic reduction make such idealized electrolysis difficult to achieve. Herein, asymmetric cross-coupling between α-chloroesters and aryl bromides is probed as a model reaction, wherein alkyl radicals are generated from the α-chloroesters through a sequential oxidative electron transfer process at the anode, while the nickel catalyst is reduced to a lower oxidation state at the cathode. Radical clock studies, cyclic voltammetry analysis, and electron paramagnetic resonance experiments support the synergistic involvement of anodic and cathodic redox events. This electrolytic method provides an alternative avenue for asymmetric catalysis that could find significant utility in organic synthesis.

A novel strategy for the N-arylation of NH-sulfoximines has been developed by merging nickel catalysis and electrochemistry (in an undivided cell), thereby providing a practical method for the construction of sulfoximine derivatives. Paired electrolysis is employed in this protocol, so a sacrificial anode is not required. Owing to the mild reaction conditions, excellent functional group tolerance and yield are achieved. A preliminary mechanistic study indicates that the anodic oxidation of a NiII species is crucial to promote the reductive elimination of a C-N bond from the resulting NiIII species at room temperature.

We describe, for the first time, two protocols for direct difluoromethylation of unactivated alkyl bromides and iodides. Reactions of alkyl iodides with TMSCF2H were mediated by a copper catalyst using CsF as the activator, while reactions of less reactive alkyl bromides required a combination of palladium and a stoichiometric amount of CuI as the catalysts. Preliminary mechanistic studies of the synergistic Pd/Cu-catalyzed difluoromethylation of alkyl bromides suggest that it proceeds likely via a Pd(I)/Pd(III) catalytic cycle.

A process for the concurrent transfer of both the NHC ligand and the difluoromethyl group from [(SIPr)Ag-(CF2H)] to PdX2 (X = Cl, OAc, and OPiv) for the preparation of [(SIPr)Pd(CF2H)X] complexes is described. These complexes were air-stable and easily underwent transmetalation with aryl pinacol boronate/reductive elimination to generate ArCF2H in high yields. Based on this discovery, the first one-pot C-H borylation and difluoromethylation process for the preparation of difluoromethylated (hetero)arenes was developed.

Light-driven water electrolysis at a semiconductor surface is a promising way to generate hydrogen from sustainable energy sources, but its efficiency is limited by the performance of available photoabsorbers. Here we report the first time investigation of covalent organic frameworks (COFs) as a new class of photoelectrodes. The presented 2D-COF structure is assembled from aromatic amine-functionalized tetraphenylethylene and thiophene-based dialdehyde building blocks to form conjugated polyimine sheets, which π-stack in the third dimension to create photoactive porous frameworks. Highly oriented COF films absorb light in the visible range to generate photoexcited electrons that diffuse to the surface and are transferred to the electrolyte, resulting in proton reduction and hydrogen evolution. The observed photoelectrochemical activity of the 2D-COF films and their photocorrosion stability in water pave the way for a novel class of photoabsorber materials with versatile optical and electronic properties that are tunable through the selection of appropriate building blocks and their three-dimensional stacking.

A photoresponsive metal organic framework material undergoes switching of its pore volume and sorption capacity. UV irradiation of the crystals causes cyclisation within the bis-thienylcyclopentene bridging ligands, thereby altering the node positions relative to one another along the Zn-L-Zn linkages. Incorporation of conformational flexibility into the dicarboxylic acid co-ligands facilitates the change in the framework geometry enforced by photocyclisation.

Covalent organic frameworks (COFs), formed by reversible condensation of rigid organic building blocks, are crystalline and porous materials of great potential for catalysis and organic electronics. Particularly with a view of organic electronics, achieving a maximum degree of crystallinity and large domain sizes while allowing for a tightly π-stacked topology would be highly desirable. We present a design concept that uses the 3D geometry of the building blocks to generate a lattice of uniquely defined docking sites for the attachment of consecutive layers, thus allowing us to achieve a greatly improved degree of order within a given average number of attachment and detachment cycles during COF growth. Synchronization of the molecular geometry across several hundred nanometers promotes the growth of highly crystalline frameworks with unprecedented domain sizes. Spectroscopic data indicate considerable delocalization of excitations along the π-stacked columns and the feasibility of donor–acceptor excitations across the imine bonds. The frameworks developed in this study can serve as a blueprint for the design of a broad range of tailor-made 2D COFs with extended π-conjugated building blocks for applications in photocatalysis and optoelectronics.

The reaction of mixtures of aryllithium regioisomers obtained either by directed lithiation or by Br/Li exchange with substoichiometric amounts of Cp2ZrCl2 proceeds with high regioselectivity. The least sterically hindered regioisomeric aryllithium is selectively transmetalated to the corresponding arylzirconium species leaving the more hindered aryllithium ready for various reactions with electrophiles. As an application, these regioselective transmetalations from Li to Zr were used to prepare all three lithiated regioisomers of 1,3-bis(trifluoromethyl) benzene.

The incorporation of side groups into a covalent organic framework (COF) backbone can be of significant importance for developing new frameworks with enhanced properties. Here we present a novel π-stacked thiophene-based COF containing a benzodithiophene building unit modified with ethoxy side chains. The resulting BDT-OEt COF is a crystalline mesoporous material featuring high surface area and accessible hexagonal pores. We further synthesized a series of COFs containing both BDT and BDT-OEt building units at different ratios. The impact of the gradual incorporation of the BDT-OEt building units into the COF backbone on the crystallinity and porosity was investigated. Furthermore, molecular dynamic simulations shed light on the possible processes governing the COF assembly from molecular building blocks.

AbstractDie Reaktion von Aryllithium‐Regioisomerengemischen, dargestellt durch direkte Lithiierung oder durch Br‐Li‐Austausch, mit substöchiometrischen Mengen an Cp2ZrCl2 verläuft mit hoher Regioselektivität. Das am wenigsten gehinderte Regioisomer wird selektiv zur entsprechenden Arylzirconiumspezies transmetalliert, wobei die stärker gehinderte Aryllithiumverbindung zurückbleibt, um weitere Reaktionen mit Elektrophilen einzugehen. Mit dieser regioselektiven Transmetallierung von Li auf Zr wurden alle drei lithiierten Regioisomere von 1,3‐Bis(trifluormethyl)benzol synthetisiert.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

[This corrects the article DOI: 10.3762/bjoc.10.291.].

The tetragonal apohost phase of p-tert-butyltetramethoxythiacalix[4]arene absorbs hydrochloric acid and iodine. These guest molecules occupy different sites in the solid-state structure - either within the small intrinsic voids of the macrocycle or within the interstitial spaces between the host molecules. This study illustrates the dynamic deformation of the host, providing strong mechanistic insight into the diffusion of guests into this seemingly non-porous material.