Induced production, synthesis, and immunomodulatory action of clostrisulfone, a diarylsulfone from clostridium acetobutylicum

The anaerobe Clostridium acetobutylicum belongs to the most important industrially used bacteria. Whereas genome mining points to a high potential for secondary metabolism in C. acetobutylicum , the functions of most biosynthetic gene clusters are cryptic. We report that the addition of supra‐physiological concentrations of cysteine triggered the formation of a novel natural product, clostrisulfone ( 1 ). Its structure was fully elucidated by NMR, MS and the chemical synthesis of a reference compound. Clostrisulfone is the first reported natural product with a diphenylsulfone scaffold. A biomimetic synthesis suggests that pentamethylchromanol‐derived radicals capture sulfur dioxide to form 1 . In a cell‐based assay using murine macrophages a biphasic and dose‐dependent regulation of the LPS‐induced release of nitric oxide was observed in the presence of 1 .Induction of the industrial anaerobe Clostridium acetobutylicum with cysteine led to the discovery of an unprecedented diarylsulfone natural product named clostrisulfone that likely results from sulfur dioxide capture by chromane‐derived radicals. Its structure was elucidated by NMR and confirmed by synthesis. The tocopherol‐related molecule exerts immunomodulatory activities (see figure). imag

Poly(2-oxazoline) glycopolymers with tunable LCST behavior

A series of thermo-responsive glyco-poly(2-oxazoline)s based on 2-ethyl-2-oxazoline and 2-(dec-9-enyl)-2-oxazoline were prepared. To study the effect of the sugar content on the solution behavior in water, two sets of copolymers with constant monomer-to-initiator ratios of 20 and 50 and varying amounts of the hydrophobic alkene functionalized monomer were synthesized. The glycopolymers were obtained by the photoaddition of 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glycopyranose onto the double bonds followed by deacetylation of the saccharide residues. Turbidimetry measurements of the respective glycopolymers revealed a decreasing cloud point temperature with increasing amount of sugar moieties, proposed to be caused by hydrogen bonding between the sugars and the polymer amide groups, which is enabled by the flexibility of the long decyl spacer. Due to the linear relationship between cloud point temperatures and the sugar content, the cloud points can be easily tailored for specific applications

Metal-Free Aryl Cross-Coupling Directed by Traceless Linkers

The metal-free, highly selective synthesis of biaryls poses a major challenge in organic synthesis. We report the scope and mechanism of a promising new approach to (hetero)biaryls by the photochemical fusion of aryl substituents tethered to a traceless linker (photosplicing). 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 the traverse of a five-membered transition state, thus warranting consistent ipso‑ipso‑coupling fidelity. 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. </div

2-Isopropenyl-2-oxazoline : a versatile monomer for functionalization of polymers obtained via RAFT

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 (Tcp = 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

2-Isopropenyl-2-oxazoline: A Versatile Monomer for Functionalization of Polymers Obtained via RAFT

2-Isopropenyl-2-oxazoline (<i>i</i>POx) 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 <i>i</i>POx with methyl methacrylate (MMA) and <i>N</i>-<i>iso</i>-propylacrylamide (N<i>i</i>PAm) was investigated resulting in two copolymer series with <i>i</i>POx content varying from 100% to 13% (PDI = 1.37 to 1.21). The P­(<i>i</i>POx-<i>stat</i>-N<i>i</i>PAm) copolymers displayed thermoresponsive behavior in water as well as phosphate buffered saline at higher temperatures in comparison to homopolymers of N<i>i</i>PAm due to the hydrophilicity of the introduced <i>i</i>POx moieties (<i>T</i>_cp = 25 to 75 °C). Futhermore, <i>i</i>POx-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