Zelkovamycin is an OXPHOS Inhibitory Member of the Argyrin Natural Product Family

Natural products (NPs) are an important inspirational source for developing drugs and chemical probes. In 1999, the group of Ōmura reported the constitutional elucidation of zelkovamycin. Although largely unrecognized so far, this NP displays structural similarities as well as differences to the argyrin NP family, a class of peptidic NPs with promising anticancer activities and diverse mode-of-action at the molecular level. By a combination of structure elucidation experiments, the first total synthesis of zelkovamycin and bioassays, the zelkovamycin configuration was determined and its previously proposed molecular structure was revised. The full structure assignment proves zelkovamycin as an additional member of the argyrins with however unique OXPHOS inhibitory properties. Zelkovamycin may therefore not only serve as a new starting point for chemical inhibitors of the OXPHOS system, but also guide customized argyrin NP isolation and biosynthesis studies.     

RhIII-Catalyzed C−H Activation of Aryl Hydroxamates for the Synthesis of Isoindolinones

Rh^III-catalyzed C−H functionalization reaction yielding isoindolinones from aryl hydroxamates and ortho-substituted styrenes is reported. The reaction proceeds smoothly under mild conditions at room temperature, and tolerates a range of functional groups. Experimental and computational investigations support that the high regioselectivity observed for these substrates results from the presence of an ortho-substituent embedded in the styrene. The resulting isoindolinones are valuable building blocks for the synthesis of bioactive compounds. They provide easy access to the natural-product-like compounds, isoindolobenzazepines, in a one-pot two-step reaction. Selected isoindolinones inhibited Hedgehog (Hh)-dependent differentiation of multipotent murine mesenchymal progenitor stem cells into osteoblasts.     

Pointlike gamma ray sources as signatures of distant accelerators of ultrahigh energy cosmic rays

We discuss the possibility of observing distant accelerators of ultrahigh energy cosmic rays in synchrotron gamma rays. Protons propagating away from their acceleration sites produce extremely energetic electrons during photopion interactions with cosmic microwave background photons. If the accelerator is embedded in a magnetized region, these electrons will emit high energy synchrotron radiation. The resulting synchrotron source is expected to be pointlike, steady, and detectable in the GeV-TeV energy range if the magnetic field is at the nanoGauss level.     

Theory of charge sensing in quantum-dot structures

Charge sensing in quantum-dot structures is studied by an exactly solvable reduced model and numerical density-matrix renormalization-group methods. Charge sensing is characterized by repeated cycling of the occupation of current-carrying states due to the capacitive coupling to trap states. In agreement with recent experiments, it results in characteristic asymmetric Coulomb-blockade peaks as well as sawtooth and domelike structures. Temperature introduces asymmetric smearing of these features and correlations in the conductance provide a fingerprint of charge sensing.     

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