2-Isopropenyl-2-oxazoline (iPOx) was polymerized for the first time via a controlled radical polymerization technique. Reversible addition–fragmentation chain transfer (RAFT) polymerization utilizing a dithiobenzoate-based chain transfer agent was employed to form a backbone that is highly reactive toward thiols and acids. Moreover, the statistical copolymerization of iPOx with methyl methacrylate (MMA) and N-iso-propylacrylamide (NiPAm) was investigated resulting in two copolymer series with iPOx content varying from 100% to 13% (PDI = 1.37 to 1.21). The P(iPOx-stat-NiPAm) copolymers displayed thermoresponsive behavior in water as well as phosphate buffered saline at higher temperatures in comparison to homopolymers of NiPAm due to the hydrophilicity of the introduced iPOx moieties (T cp = 25 to 75 °C). Futhermore, iPOx-based (co)polymers were functionalized by polymer analogous addition reactions with thiophenol, benzoic acid and 4-azidobenzoic acid in high conversions (74–100%). The latter adduct represented a suitable building block for the synthesis of a graft copolymer consisting of a PMMA backbone and poly(2-ethyl-2-oxazoline) (PEtOx) side chains via copper-catalyzed azide–alkyne cycloaddition (CuAAC) of PEtOx with alkyne terminus.

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Many pharmaceuticals feature biaryl motifs that are crucial for their binding to the target. Yet, benchmark methods for selective cross-couplings rely on highly toxic heavy metal catalysts, which are unfavorable in the synthesis of pharmaceuticals. Metal-free coupling reactions, on the other hand, may require harsh conditions and lack selectivity. We report a novel, metal-free cross-coupling reaction that involves the tethering of two phenyl groups by a temporary, traceless sulfonamide linker that directs a photochemical aryl fusion into a single coupling product. The perfect regio- and chemoselectivity of the reaction could be rationalized by a cyclic intermediate, which fragments into the biaryl and volatile side products. Using a flow reactor, we synthesized numerous substituted biaryl building blocks for important therapeutics in high yields, such as antibiotics, antitumor, neuroprotective and cholesterol-lowering agents as well as antiarthritic non-steroidal antiinflammatory drugs (NSAIDs). The new method was successfully employed in a total synthesis of cannabinol, an important analgesic and antiemetic therapeutic. We also report a metal-free synthesis of key building blocks used for the preparation of sartans, antihypertensive agents that rank among the top blockbuster drugs worldwide. This safe and convenient protocol is a valuable alternative for the widely used metal-dependent aryl cross-coupling methods.

Summary Aspergillus fumigatus is an opportunistic human pathogenic fungus causing life-threatening infections in immunocompromised patients. Adaptation to different habitats and also virulence of the fungus depends on signal perception and transduction by modules such as the cyclic AMP-dependent protein kinase A (PKA) pathway. Here, by transcriptome analysis, 632 differentially regulated genes of this important signaling cascade were identified, including 23 putative transcriptional regulators. The highest upregulated transcription factor gene was located in a previously unknown secondary metabolite gene cluster, which we named fmp, encoding an incomplete nonribosomal peptide synthetase, FmpE. Overexpression of the regulatory gene fmpR using the TetOn system led to the specific expression of the other six genes of the fmp cluster. Metabolic profiling of wild type and fmpR overexpressing strain by HPLC-DAD and HPLCHRESI-MS and structure elucidation by NMR led to identification of 5-benzyl-1H-pyrrole-2-carboxylic acid, which we named fumipyrrole. Fumipyrrole was not described as natural product yet. Chemical synthesis of fumipyrrole confirmed its structure. Interestingly, deletion of fmpR or fmpE led to reduced growth and sporulation of the mutant strains. Although fmp cluster genes were transcribed in infected mouse lungs, deletion of fmpR resulted in wild-type virulence in a murine infection model.

The metal‐free, highly selective synthesis of biaryls poses a major challenge in organic synthesis. The scope and mechanism of a promising new approach to (hetero)biaryls by the photochemical fusion of aryl substituents tethered to a traceless sulfonamide linker (photosplicing) are reported. Interrogating photosplicing with varying reaction conditions and comparison of diverse synthetic probes (40 examples, including a suite of heterocycles) showed that the reaction has a surprisingly broad scope and involves neither metals nor radicals. Quantum chemical calculations revealed that the C−C bond is formed by an intramolecular photochemical process that involves an excited singlet state and traversal of a five‐membered transition state, and thus consistent ipso–ipso coupling results. These results demonstrate that photosplicing is a unique aryl cross‐coupling method in the excited state that can be applied to synthesize a broad range of biaryls.