Probing o‐Diphenylphosphanyl Benzoate (o‐DPPB)‐Directed CC Bond Formation: Total Synthesis of Dictyostatin

Herein, we report a robust total synthesis of dictyostatin. This polyketide natural product has attracted much attention because of its impressive antiproliferative activity against several human cancer‐cell lines. We accomplished its synthesis in a highly convergent manner from three fragments of equal complexity, which were prepared on multigram scale. The southern and northwestern subunits were constructed through application of our o‐DPPB‐directed hydroformylation and allylic substitution methodology, respectively. These methods generated the C6 and C14 stereocenters of dictyostatin with good diastereoselectivities and simultaneously allowed further elaboration of the fragments by Wittig olefination and Sharpless asymmetric epoxidation, respectively. The compelling performance of the hydroformylation and allylic substitution with regard to practicability, selectivity, and scale underline their value for the construction of propionate motifs.     

Synthesis of Alkynylated Benzo[a]naphtho[2,3‐i]phenazine Derivatives

Thermal condensation of 2,3‐diamino‐1,4‐(bistriisopropylsilylethynyl)benzene, ‐naphthalene,‐anthracene, and ‐benzothiadiazole substrates with 1,2‐naphthalenedione forms bent benzophenazine‐type heteroarenes in a one‐step reaction in good to excellent yields. The targets are investigated by UV/Vis spectroscopy, cyclic voltammetry, and single‐crystal X‐ray crystallography. The packing of the targets in the solid state follows either a herringbone or a brick wall motif. In the case of 8,13‐bis(triisopropylsilylethynyl)dibenzo[a,i]phenazine, polymorphs with either packing result.     

Chemoenzymatic Synthesis of Nonasulfated Tetrahyaluronan with a Paramagnetic Tag for Studying Its Complex with Interleukin‐10

Implants and artificial biomaterials containing sulfated hyaluronans have been shown to improve the healing of injured skin and bones. It is hypothesized that these effects are mediated by the binding of sulfated glycosaminoglycans (GAGs) to growth factors and cytokines, resulting in the sequestering of proteins to the wound healing site and in modulated protein activity. Given that no direct synthetic access to sulfated oligohyaluronans has been available, little is known about their protein binding and the structure of the resulting protein complexes. Here, the chemoenzymatic preparation of oligohyaluronans on the gram scale is described. Oligohyaluronans are converted into anomeric azides at the reducing end, enabling the attachment of analytical labels through an anomeric ligation reaction. A nonasulfated tetrahyaluronan–ethylenediaminetetraacetic acid derivative has been produced and used as a paramagnetic tag for the elucidation of the complex of this ligand with interleukin‐10 using paramagnetic relaxation enhancement NMR analysis. The metal ion position is resolved with 1.0 Å, enabling a refined structural model of the complex.     

Self‐Assembled Cyclic d,l‐α‐Peptides as Generic Conformational Inhibitors of the α‐Synuclein Aggregation and Toxicity: In Vitro and Mechanistic Studies

Many peptides and proteins with large sequences and structural differences self‐assemble into disease‐causing amyloids that share very similar biochemical and biophysical characteristics, which may contribute to their cross‐interaction. Here, we demonstrate how the self‐assembled, cyclic d,l ‐α‐peptide CP‐2 , which has similar structural and functional properties to those of amyloids, acts as a generic inhibitor of the Parkinson′s disease associated α‐synuclein (α‐syn) aggregation to toxic oligomers by an ?off‐pathway“ mechanism. We show that CP‐2 interacts with the N‐terminal and the non‐amyloid‐β component region of α‐syn, which are responsible for α‐syn′s membrane intercalation and self‐assembly, thus changing the overall conformation of α‐syn. CP‐2 also remodels α‐syn fibrils to nontoxic amorphous species and permeates cells through endosomes/lysosomes to reduce the accumulation and toxicity of intracellular α‐syn in neuronal cells overexpressing α‐syn. Our studies suggest that targeting the common structural conformation of amyloids may be a promising approach for developing new therapeutics for amyloidogenic diseases.     

Photoelectrochemical CO2 Reduction by a Molecular Cobalt(II) Catalyst on Planar and Nanostructured Si Surfaces

In the presence of a molecular Co^II catalyst, CO₂ reduction occurred at much less negative potentials on Si photoelectrodes than on an Au electrode. The addition of 1 % H₂O significantly improved the performance of the Co^II catalyst. Photovoltages of 580 and 320 mV were obtained on Si nanowires and a planar Si photoelectrode, respectively. This difference likely originated from the fact that the multifaceted Si nanowires are better in light harvesting and charge transfer than the planar Si surface.