Lugdunomycin, an Angucycline-Derived Molecule with Unprecedented Chemical Architecture

The angucyclines form the largest family of polycyclic aromatic polyketides, and have been studied extensively. Herein, we report the discovery of lugdunomycin, an angucycline-derived polyketide, produced by Streptomyces species QL37. Lugdunomycin has unique structural characteristics, including a heptacyclic ring system, a spiroatom, two all-carbon stereocenters, and a benzaza-[4,3,3]propellane motif. Considering the structural novelty, we propose that lugdunomycin represents a novel subclass of aromatic polyketides. Metabolomics, combined with MS-based molecular networking analysis of Streptomyces sp. QL37, elucidated 24 other rearranged and non-rearranged angucyclines, 11 of which were previously undescribed. A biosynthetic route for the lugdunomycin and limamycins is also proposed. This work demonstrates that revisiting well-known compound families and their producer strains still is a promising approach for drug discovery

Disappearing disorder

Single crystal X-ray diffraction is the method of choice to resolve difficult solid-state problems. This is exemplified by analysis of three disordered structures that cease to be disordered depending on the circumstances. Interesting research questions of relevance for the pharmaceutical industry, including possible issues of intellectual property, emerge from disappearing disorder phenomena. Its relationship to polymorphism is discussed, and the term ‘archetype structure’ that includes both polymorphs and disorder components is recommended for use. X-ray structural studies reported here benefit from refinement with aspherical scattering factors that improve accuracy and precision of the results, thereby providing the confidence required in interpreting comparably small residual electron density features. Full understanding of the mechanism of how disorder can come into existence and disappear with temperature or time (pressure being another factor not exploited here) requires computing the relative energy differences of archetype structures by ONIOM cluster or solid-state computations

A functionalized Ge3-compound with a dual character of the central germanium atom

Deutsche Forschungs gemeinschaft [RO 224/60-1]; China Scholarship Council (CSC)(cAAC) Ge(GeL)(2) (1) (cAAC = cyclic alkyl(amino) carbene; L = PhC-(tBuN)(2)), a functionalized Ge-3-compound was prepared. Quantum mechanical studies on 1 show a reciprocal relationship between the electronic state of the central tri-coordinated Ge atom and its reactivity towards protons, viz. tetravalent Ge(0) in terms of bonding and divalent Ge(0) in terms of reactivity. Thus the central Ge atom can be considered as having a hidden but highly reactive lone pair of electrons. However, the terminal Ge atoms can be considered as tri-coordinated divalent Ge(I) with an active lone pair of electrons