Metal-Free Twofold Electrochemical C−H Amination of Activated Arenes: Application to Medicinally Relevant Precursor Synthesis

The efficient production of many medicinally or synthetically important starting materials suffers from wasteful or toxic precursors for the synthesis. In particular, the aromatic non-protected primary amine function represents a versatile synthetic precursor, but its synthesis typically requires toxic oxidizing agents and transition metal catalysts. The twofold electrochemical amination of activated benzene derivatives via Zincke intermediates provides an alternative sustainable strategy for the formation of new C−N bonds of high synthetic value. As a proof of concept, we use our approach to generate a benzoxazinone scaffold that gained attention as a starting structure against castrate-resistant prostate cancer. Further improvement of the structure led to significantly increased cancer cell line toxicity. Thus, exploiting environmentally benign electrooxidation, we present a new versatile and powerful method based on direct C−H activation that is applicable for example the production of medicinally relevant compounds.     

Inverse colloidal crystal membranes for hydrophobic interaction membrane chromatography

A collaborative study on the robustness and portability of a capillary electrophoresis‐mass spectrometry method for peptide mapping was performed by an international team, consisting of 13 independent laboratories from academia and industry. All participants used the same batch of samples, reagents and coated capillaries to run their assays, whereas they utilized the capillary electrophoresis‐mass spectrometry equipment available in their laboratories. The equipment used varied in model, type and instrument manufacturer. Furthermore, different types of sheath‐flow capillary electrophoresis–mass spectrometry interfaces were used. Migration time, peak height and peak area of ten representative target peptides of trypsin‐digested bovine serum albumin were determined by every laboratory on two consecutive days. The data were critically evaluated to identify outliers and final values for means, repeatability (precision within a laboratory) and reproducibility (precision between laboratories) were established. For relative migration time the repeatability was between 0.05 and 0.18% RSD and the reproducibility between 0.14 and 1.3% RSD. For relative peak area repeatability and reproducibility values obtained were 3–12 and 9–29% RSD, respectively. These results demonstrate that capillary electrophoresis‐mass spectrometry is robust enough to allow a method transfer across multiple laboratories and should promote a more widespread use of peptide mapping and other capillary electrophoresis‐mass spectrometry applications in biopharmaceutical analysis and related fields.     

Shortest Paths with Shortest Detours

This paper is concerned with a biobjective routing problem, called the shortest path with shortest detour problem, in which the length of a route is minimized as one criterion and, as second, the maximal length of a detour route if the chosen route is blocked is minimized. Furthermore, the relation to robust optimization is pointed out, and we present a new polynomial time algorithm, which computes a minimal complete set of efficient paths for the shortest path with shortest detour problem. Moreover, we show that the number of nondominated points is bounded by the number of arcs in the graph.     

CycloSiFA: The Next Generation of Silicon-Based Fluoride Acceptors for Positron Emission Tomography (PET)

The ring-opening Si-fluorination of a variety of azasilole derivatives cyclo-1-(iPr₂Si)−4-X−C₆H₃−2-CH₂NR ( 4 : R=2,6-iPr₂C₆H₃, X=H; 4 a : R=2,4,6-Me₃C₆H₂, X=H; 9 : R=2,6-iPr₂C₆H₃, X=tBuMe₂SiO; 10 : R=2,6-iPr₂C₆H₃, X=OH; 13 : R=2,6-iPr₂C₆H₃, X=HCCCH₂O; 22 : R=2,6-iPr₂C₆H₃, X=tBuMe₂SiCH₂O) with different ¹⁹F-fluoride sources was studied, optimized and the experience gained was used in a translational approach to create a straightforward ¹⁸F-labelling protocol for the azasilole derivatives [¹⁸F] 6 and [¹⁸F] 14 . The latter constitutes a potential clickable CycloSiFA prosthetic group which might be used in PET tracer development using Cu-catalysed triazole formation. Based on our findings, CycloSiFA has the potential to become a new entry into non-canonical labelling methodologies for radioactive PET tracer development.     

Synthesis of 1,3-Dioxan-2-ones by Photo-Aerobic Selenium-π-Acid Multicatalysis

An expedient method for the synthesis of cyclic carbonates from homoallylic carbonic acid esters by means of photo-aerobic selenium-π-acid multicatalysis is reported. Until now, conceptually related methods commonly relied either on the stoichiometric addition of electrophiles onto the substrate's alkene moiety or the presence of pre-installed leaving groups in allylic position of said alkene to – in part, catalytically – initiate an intramolecular attack by an adjacent carbonic acid ester group. In sharp contrast, the current study shows that the C−C double bond of homoallylic carbonic acid esters can be directly activated by the catalytic interplay of a pyrylium dye and a diselane using ambient air as the sole oxidant and visible light as an energy source.     

An interlaboratory capillary zone electrophoresis-UV study of various monoclonal antibodies,instruments, and ε-aminocaproic acid lots

Capillary zone electrophoresis ultraviolet (CZE-UV) has become increasingly popular for the charge heterogeneity determination of mAbs and vaccines. The ε-aminocaproic acid (eACA) CZE-UV method has been used as a rapid platform method. However, in the last years, several issues have been observed, for example, loss in electrophoretic resolution or baseline drifts. Evaluating the role of eACA on the reported issues, various laboratories were requested to provide their routinely used eACA CZE-UV methods, and background electrolyte compositions. Although every laboratory claimed to use the He et al. eACA CZE-UV method, most methods actually deviate from He's. Subsequently, a detailed interlaboratory study was designed wherein two commercially available mAbs (Waters’ Mass Check Standard mAb [pI 7] and NISTmAb [pI 9]) were provided to each laboratory, along with two detailed eACA CZE-UV protocols for a short-end, high-speed, and a long-end, high-resolution method. Ten laboratories participated each using their own instruments, and commodities, showing excellence method performance (relative standard deviations [RSDs] of percent time-corrected main peak areas from 0.2% to 1.9%, and RSDs of migration times from 0.7% to 1.8% [n = 50 per laboratory], analysis times in some cases as short as 2.5 min). This study clarified that eACA is not the main reason for the abovementioned variations.     

A General and Highly Selective Palladium‐Catalyzed Hydroamidation of 1,3‐Diynes

A chemo‐, regio‐, and stereoselective mono‐hydroamidation of (un)symmetrical 1,3‐diynes is described. Key for the success of this novel transformation is the utilization of an advanced palladium catalyst system with the specific ligand Neolephos. The synthetic value of this general approach to synthetically useful α‐alkynyl‐α, β‐unsaturated amides is showcased by diversification of several structurally complex molecules and marketed drugs. Control experiments and density‐functional theory (M06L‐SMD) computations also suggest the crucial role of the substrate in controlling the regioselectivity of unsymmetrical 1,3‐diynes.     

Investigations of the Vicarious C‐Aminations of 5,7‐Dinitrobenzotriazole and 4,6‐Dinitrobenzotriazol‐3‐ium‐1‐oxide and Their Energetic Properties

This combined experimental and theoretical study details the vicarious nucleophilic substitution by amination of 5,7‐dinitrobenzotriazol ( 1 ) and 4,6‐dinitrobenzotriazole‐3‐ium‐1‐oxide ( 4 ) with trimethylhydrazinium iodide to afford the new corresponding one‐ and two‐time aminated compounds and investigations of its mechanism by EPR spectroscopy. The preferred position for the first amination is computed by spin density population and verified by X‐ray crystallography. The zwitterionic structure of 4 is investigated in solution by ¹H NMR spectroscopy and in solid state by X‐ray diffraction. Furthermore, the crystal structure of 1 is presented. The energetic behavior of the aminated products as well as the starting materials 1 and 4 was investigated, regarding sensitivities and performance.