Visible Light‐Promoted Decarboxylative Di‐ and Trifluoromethylthiolation of Alkyl Carboxylic Acids

Described herein is a new and straightforward decarboxylative di‐ and trifluoromethylthiolation of alkyl carboxylic acids promoted by visible light. This approach enables the synthesis of biologically relevant alkyl SCF₂H and SCF₃ compounds from cheap and abundant carboxylic acids. The method is operationally simple, using irradiation from household light sources, and its mild reaction conditions make it tolerant of a range of functional groups. The strategy employs electrophilic phthalimide‐derived di‐ and trifluoromethylthiolation reagents and exploits the ability of the imidyl radical to carry a radical chain.     

Bifunctional Diaminoterephthalate Scaffolds as Fluorescence Turn‐On Probes for Thiols

The fluorescent diaminoterephthalate scaffold was equipped by amidation with three types of reactive functions: thiols for metal‐surface binding, alkynes for click reactions, and maleimides for ligation with proteins. Starting from a succinyl succinate derivative with two orthogonally cleavable ester functions, three monoamides (38–57 % yield over three steps) and two bisamides (19 and 25 % yield over five steps) were prepared. Although alkyne and thiol derivatized compounds showed reasonable luminescence behavior (Φ≈1–4 %), the fluorescence was quenched by the maleimide moiety. It was turned on (10‐ to 20‐fold increase of fluorescence quantum yield) by conjugate addition of thiols.     

"One-pot" tandem C-H borylation/1,4-conjugate addition/reduction sequence

A microwave-assisted, one-pot, iridium-catalyzed aromatic C-H borylation/rhodium-catalyzed 1,4-conjugate addition sequence provides a highly robust protocol suitable for high-throughput array synthesis. Selective formation of either β-aryl-substituted ketones or the corresponding alcohols can be achieved in good overall yields by simple variation of the reaction conditions.     

Thermal and long-term stability of fast-ion-irradiation-induced refractive index changes in lithium niobate crystals

Irradiation of congruently melting, nominally undoped lithium niobate crystals (LiNbO₃) with high-energy, low-mass ³He ions, which are transmitted through the crystal, causes large and stable changes of the refractive index. In the irradiated regions, the extraordinary index is increased whereas the ordinary index is diminished. The decay of these changes upon annealing treatments up to 400°C is investigated, exhibiting a strongly non-monoexponential decay behaviour. Long-term measurements of the refractive index changes yield no pattern erasure on a timescale of four years.     

1,3,5-Triazepane-2,6-diones as structurally diverse and conformationally constrained dipeptide mimetics: identification of malaria liver stage inhibitors from a small pilot library

The development of the 1,3,5-triazepane-2,6-dione system as a novel, conformationally restricted, and readily accessible class of dipeptidomimetics is reported. The synthesis of the densely functionalized 1,3,5-triazepane-2,6-dione skeleton was achieved in only four steps from a variety of simple linear dipeptide precursors. To extend the practical value of 1,3,5-triazepane-2,6-diones, a general polymer-assisted solution-phase synthesis approach amenable to library production in a multiparallel format was developed. The conformational preferences of the 1,3,5-triazepane-2,6-dione skeleton were investigated in detail by NMR spectroscopy and X-ray diffraction. The ring exhibits a characteristic folded conformation which was compared to that of related dipeptide-derived scaffolds including the more planar 2,5-diketopiperazine (DKP). Molecular and structural diversity was increased further through post-cyclization appending operations at urea nitrogens. Preliminary biological screens of a small collection of 1,3,5-triazepane-2,6-diones revealed inhibitors of the underexplored malaria liver stage and suggest strong potential for this dipeptide-derived scaffold to interfere with and to modulate biological pathways.     

A fluorescent derivatization method of proteins for the detection of low‐level impurities by microchip capillary gel electrophoresis

A novel pre‐chip fluorescent derivatization method is presented for protein sizing and quantification by microchip CGE. The derivatization reaction employed a water‐soluble and stable fluorescent dye and was performed under conditions that favored the formation of homogeneous reaction products. The method delivered in terms of protein sizing similar results as microchip CGE with on‐chip staining but showed an extended linear dynamic range for protein quantification encompassing four orders of magnitude. The sensitivity of the method was similar to standard silver‐stained planar gels. The characterization of derivatization reaction products by MS and preparative isoelectric focusing indicated that a constant degree of dye molecule tagging was obtained over a broad range of protein/dye ratios. The method allowed detecting and quantifying an impurity spiked into an antibody preparation down to a level of 0.05%. Advantages of this method compared with CGE approaches with pre‐column derivatization include a shorter analysis time and an increased robustness and ease of use.