Learning from natures's lessons: development of bioinspired catalysts for selective oxidative halogenations and their application for the creation of potent biomedical agents

• Applicant: Professorin Dr. Tanja Gulder
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2012 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 232194327

• Final Report Year: 2023

Final Report Abstract

The halogenation of organic molecules is one of the most common methods for the functionalization of substrates, as halogen atoms often serve as good handles for further chemical manipulations. In addition, halogenated compounds themselves play an important role in pharmaceuticals, agrochemicals, and materials. Electrophilic halogenation of alkenes constitutes the oldest and still most frequently used halogenation procedure. Despite the broad application of halogen-containing compounds, common strategies for the formation of carbon-halogen (C,X) bonds often suffer from severe drawbacks such as stereo- and regioselectivity issues as well as environmental and/or safety concerns. Within the Emmy-Noether funding, we addressed these problems by taking Nature as an inspiration. By exploring, harnessing, and imitating Nature’s concepts, mild, generally applicable, and selective methods have become available, reaching from biocatalysis, peptide-metal and hypervalent iodane catalysis and reagents to transformations in confined space employing F-alcohol-Lewis base supramolecular, catalytically active assemblies. Utilizing these methods, a rich diversity of novel chemical structures was obtained that are often not accessible by standard strategies, and their usefulness was demonstrated by the synthesis of natural products, antiinfectives, and diagnostics.

Publications

• A Fluorination/Aryl Migration/Cyclization Cascade for the Metal‐Free Synthesis of Fluoro‐Benzoxazepines. Chemistry – A European Journal, 22(11), 3660-3664.
  Ulmer, Anna; Brunner, Christoph; Arnold, Andreas M.; Pöthig, Alexander & Gulder, Tanja
  
• Atom‐Economic Electron Donors for Photobiocatalytic Halogenations. ChemCatChem, 10(18), 3960-3963.
  Seel, Catharina Julia; Králík, Antonín; Hacker, Melanie; Frank, Annika; König, Burkhard & Gulder, Tanja
  
• Fluorine as a Traceless Directing Group for the Regiodivergent Synthesis of Indoles and Tryptophans. Journal of the American Chemical Society, 140(40), 13034-13041.
  Andries-Ulmer, Anna; Brunner, Christoph; Rehbein, Julia & Gulder, Tanja
  
• NXS, Morpholine, and HFIP: The Ideal Combination for Biomimetic Haliranium-Induced Polyene Cyclizations. Journal of the American Chemical Society, 140(12), 4344-4353.
  Arnold, Andreas M.; Pöthig, Alexander; Drees, Markus & Gulder, Tanja
  
• α-Functionalization of Ketones via a Nitrogen Directed Oxidative Umpolung. Journal of the American Chemical Society, 142(49), 20577-20582.
  Kiefl, Gabriel M. & Gulder, Tanja
  
• 3D‐Non‐destructive Imaging through Heavy‐Metal Eosin Salt Contrast Agents. Chemistry – A European Journal, 27(14), 4561-4566.
  Busse, Madleen; Marciniszyn, Jaroslaw P.; Ferstl, Simone; Kimm, Melanie A.; Pfeiffer, Franz & Gulder, Tanja
  
• Biosynthesis of cyanobacterin, a paradigm for furanolide core structure assembly. Nature Chemical Biology, 18(6), 652-658.
  D’Agostino, Paul M.; Seel, Catharina J.; Ji, Xiaoqi; Gulder, Tanja & Gulder, Tobias A. M.
  
• Biomimetic chlorine-induced polyene cyclizations harnessing hypervalent chloroiodane–HFIP assemblies. Chemical Science, 14(14), 3907-3912.
  Binder, Julia; Biswas, Aniruddha & Gulder, Tanja
  
• Enzyme-like polyene cyclizations catalyzed by dynamic, self-assembled, supramolecular fluoro alcohol-amine clusters. Nature Communications, 14(1).
  Arnold, Andreas M.; Dullinger, Philipp; Biswas, Aniruddha; Jandl, Christian; Horinek, Dominik & Gulder, Tanja
  
• Hypervalent Fluoro-iodane-Triggered Semipinacol Rearrangements: Synthesis of α-Fluoro Ketones. Organic Letters, 25(35), 6560-6565.
  Zhao, Pengyuan; Wang, Wanying & Gulder, Tanja