Supplementary material for the article: Bihelovic, F.; Stichnoth, D.; Surup, F.; Müller, R.; Trauner, D. Total Synthesis of Crocagin A. Angewandte Chemie - International Edition 2017, 56 (42), 12848–12851. https://doi.org/10.1002/anie.201612641

Supporting information for: [https://doi.org/10.1002/anie.201612641]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2532

Multiformin-Type Azaphilones Prevent SARS-CoV-2 Binding to ACE2 Receptor

Protein microarray screenings identified fungal natural products from the azaphilone family as potent inhibitors of SARS-CoV-2 spike protein binding to host ACE2 receptors. Cohaerin F, as the most potent substance from the cohaerin group, led to more than 50% less binding of ACE2 and SARS-CoV-2 spike protein. A survey for structurally related azaphilones yielded the structure elucidation of six new multiformins E–J (10–15) and the revision of the stereochemistry of the multiformins. Cohaerin and multiformin azaphilones (1–5, 8, 12) were assessed for their activity in a cell-based infection assay. Calu-3 cells expressing human ACE2 receptor showed more than 75% and 50% less infection by SARS-CoV-2 pseudotyped lentivirus particles after treatment with cohaerin C (1) and cohaerin F (4), respectively. Multiformin C (8) and G (12) that nearly abolished the infection of cells. Our data show that multiformin-type azaphilones prevent the binding of SARS-CoV-2 to the cell entry receptor ACE2

Biosynthesis of Crocacin Involves an Unusual Hydrolytic Release Domain Showing Similarity to Condensation Domains

SummaryThe crocacins are potent antifungal and cytotoxic natural compounds from myxobacteria of the genus Chondromyces. Although total synthesis approaches have been reported, the molecular and biochemical basis guiding the formation of the linear crocacin scaffold has remained unknown. Along with the identification and functional analysis of the crocacin biosynthetic gene cluster from Chondromyces crocatus Cm c5, we here present the identification and biochemical characterization of an unusual chain termination domain homologous to condensation domains responsible for hydrolytic release of the product from the assembly line. In particular, gene inactivation studies and in vitro experiments using the heterologously produced domain CroK-C2 confirm this surprising role giving rise to the linear carboxylic acid. Additionally, we determined the kinetic parameters of CroK-C2 by monitoring hydrolytic cleavage of the substrate mimic N-acetylcysteaminyl-crocacin B using an innovative high-performance liquid chromatography mass spectrometry-based assay

Supplementary material for the article: Bihelovic, F.; Stichnoth, D.; Surup, F.; Müller, R.; Trauner, D. Total Synthesis of Crocagin A. Angewandte Chemie - International Edition 2017, 56 (42), 12848–12851. https://doi.org/10.1002/anie.201612641

Supporting information for: [https://doi.org/10.1002/anie.201612641]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2532

Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology.

Funder: This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding ProgramMeroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects

Elsinopirins A–D, Decalin Polyketides from the Ascomycete Elsinoё pyri

In course of our screening for new secondary metabolites from ecological niche specialized, phytopathogenic fungi, the plant pathogen Elsinoё pyri, strain 2203C, was found to produce four novel compounds (1–4), which were named elsinopirins A–D, in addition to the known metabolite elsinochrome A (5). After isolation by preparative high-performance liquid chromatography (HPLC), their structures, including relative stereochemistry, were elucidated by 1D and 2D nuclear magnetic resonance (NMR) and mass spectrometry (MS) data. Finally, absolute stereochemistry was assigned by chemical shifts of Mosher’s esters (α-methoxy-α-trifluoromethylphenylacetic acid; MTPA) derivatives of elsinopirin B (2). The compounds were found to be devoid of significant antibacterial, antifungal, and cytotoxic activities

Metagenome Technology for Drug Discovery and Studies of the Iromycins from Streptomyces sp.

Gegenstand der Dissertation sind die Suche nach bioaktiven Naturstoffen mittels Screening sowie Untersuchungen zur Naturstoffgruppe der Iromycine zu Fragen der Biosynthese, biologischen Aktivität und ökologischen Zusammenhängen. Eine Metagenombank aus der mikrobiellen Symbiontenfraktion des Schwamms Aplysina aerophoba wurde hinsichtlich der Bildung von Sekundärstoffen untersucht. Etablierung eines chemischen und biologischen Screenings führte zur Isolierung und Charakterisierung von Sekundärstoffen. Brevinsäure und Tryptanthrin sind literaturbekannte Verbindungen. Für die neue Struktur mit 1,4-Naphtochinongrundgerüst, die weder als Naturstoff noch als Syntheseprodukt beschrieben war, wurde der Name Brevinsulfoxid vorgeschlagen. Die antimikrobielle Aktivität der Naturstoffe wurde spezifiziert. Eine Totalsynthese wurde etabliert und so größere Mengen von Brevinsäure und Brevinsulfoxid hergestellt. Die Biosynthese der Iromycine, die von Streptomyces sp. Dra17 produziert werden, wurde durch Fütterungsexperimente mit Isotopen-markierten Verbindungen erfolgreich untersucht. Vier weitere Mitglieder der Iromycin-Familie wurden identifiziert und als Iromycin C bis F benannt. Mittels Zugabe von Enzyminhibitoren wurde ein oxidativer Abbau des Iromycin A bewiesen. Durch ein Fütterungsexperiment wurde gezeigt, dass die Biosynthese des Thaxtomin A durch die inhibitorische Wirkung des Iromycin A auf der Ebene der bakteriellen NO-Synthase beeinflusst wird. Die Inhibitionswirkung der Iromycine auf die NO-Synthase und den Komplex I der Atmungskette wurde im Forschungsverbund untersucht. Die Struktur-Wirkungs-Beziehungen der Inhibition des Komplex I durch die Iromycin-Familie wurde durch partialsynthetische Derivate detailliert beschrieben

Secondary Metabolites from Fungi—In Honor of Prof. Dr. Ji-Kai Liu’s 60th Birthday

It is our pleasure and privilege to serve as Guest Editors for this Special Issue of the Journal of Fungi in honor of Professor Ji-Kai Liu’s 60th birthday [...

Antifungal Sesquiterpenoids, Rhodocoranes, from Submerged Cultures of the Wrinkled Peach Mushroom, Rhodotus palmatus.

Seven previously unknown sesquiterpenoids and norsesquiterpenoids, rhodocoranes F-L (1-7), were isolated from the fermentation broth of the basidiomycete Rhodotus palmatus. Their structures were elucidated utilizing 1D and 2D NMR techniques as well as HRESIMS; they are unusual noracorane, spiro[4.4]nonene, and acorane-type sesquiterpenoids. They include the first naturally occurring cyclopentylidenefuranones (3-5) and the new tricyclic scaffold of 7. Metabolites 1-7 exhibited a general mild antimycotic activity, while 1-3 also displayed cytotoxic effects

Rickicaryophyllane A, a Caryophyllane from the Ascomyceteous Fungus Hypoxylon rickii and a 10-Norbotryane Congener.

Herein we report the isolation from Hypoxylon rickii of a new sesquiterpenoid (1) with a caryophyllane skeleton. The planar structure of 1 was elucidat ed by NMR and HRMS data as the 1,12-dihydro-l-hydroxyl derivative of caryophyllenol-I, for which we propose the name rickicaryophyllane A. Its relative stereochemistry was assigned with a series of ID NOESY experiments, while the IR,2S,5R,9R absolute configuration was demonstrated by Mosher's analysis. Besides, we isolated 3-(hydroxymethyl)-1,1,3,5-tetramethyl-1,2,3,5,6,7-hexahydro-4H-inden-4-one (2) as a new 10-norbotryane derivative and the known metabolite orcacetophenone (3)