Multidrug-resistant
pathogens such as Burkholderia
cenocepacia have become a hazard in the context of
healthcare-associated infections, especially for patients admitted
with cystic fibrosis or immuno-compromising conditions. Like other
opportunistic Gram-negative bacteria, this pathogen establishes virulence
and biofilms through lectin-mediated adhesion. In particular, the superlectin BC2L-C is believed to cross-link human epithelial
cells to B. cenocepacia during pulmonary
infections. We aimed to obtain glycomimetic antagonists able to inhibit
the interaction between the N-terminal domain of
BC2L-C (BC2L-C-Nt) and its target fucosylated human oligosaccharides.
In a previous study, we identified by fragment virtual screening and
validated a small set of molecular fragments that bind BC2L-C-Nt in
the vicinity of the fucose binding site. Here, we report the rational
design and synthesis of bifunctional C- or N-fucosides, generated by connecting these fragments to
a fucoside core using a panel of rationally selected linkers. A modular
route starting from two key fucoside intermediates was implemented
for the synthesis, followed by evaluation of the new compounds as
BC2L-C-Nt ligands with a range of techniques (surface plasmon resonance,
isothermal titration calorimetry, saturation transfer difference NMR,
differential scanning calorimetry, and X-ray crystallography). This
study resulted in a hit molecule with an order of magnitude gain over
the starting methyl fucoside and in two crystal structures of antagonist/lectin
complexes.
Dearomative cycloadditions are a powerful tool to access a large chemical space exploiting simple and ubiquitous building blocks. The energetic burden due to the loss of aromaticity has however greatly limited their synthetic potential. We devised a general intramolecular method that overcomes these limitations thanks to the photosensitization of allenamides. The visible-light-promoted process gives complex [2.2.2]-(hetero)-bicyclooctadienes at room temperature, likely through the stabilization of transient (bi)radicals by naphthalene. The reaction tolerates several valuable functionalities, offering a convenient handle for a myriad of applications, including original isoindoles and metal complexes.
Dearomative cycloadditions are a powerful tool to access a large chemical space exploiting simple and ubiquitous building blocks. The energetic burden due to the loss of aromaticity has however greatly limited their synthetic potential. We devised a general intramolecular method that overcomes these limitations thanks to the photosensitization of allenamides. The visible‐light‐promoted process gives complex [2.2.2]‐(hetero)‐bicyclooctadienes at room temperature, likely through the stabilization of transient (bi)radicals by naphthalene. The reaction tolerates several valuable functionalities, offering a convenient handle for a myriad of applications, including original isoindoles and metal complexes.
We present herein the first synthesis of tetrahydropyranes promoted by a silver salt. Cinnamyl ethers undergo a formal dimerization affording the target heterocycle via sequential C-O bond cleavage/C-H bond functionalization....
The focus of analysis is the reconstruction of the relationship between the philosopher and sociologist Max Horkheimer (1895–1973) and Hans Simmel (1891–1943), Georg Simmel’s first son. Its basis is an unpublished folder at the Universitätsarchiv, Frankfurt am Main. Under review is the attempt by Horkheimer to arrange a visa for Hans Simmel to travel to the US. On the one hand, a testimony is revealed of an intellectual debt (Horkheimer’s to Georg Simmel), which was transformed into a biographical debt toward Hans; on the other hand, we sketch a tragic link with the rise of the Nazi party and the consequences of the persecution and diaspora of Jews from Germany, as well as the Institute for Social Research (New York) commitments to help German intellectuals. Consequently, there are two principal aims: firstly, to reconstruct the biographical events which connect Hans Simmel and Max Horkheimer at a specific period (1936–1943), furnishing details about concrete aspects of their historical situation; secondly, in the background we examine the ambivalent relationship between Georg Simmel’s thought and the former Frankfurt School authors, who appreciated Simmel’s innovative style, yet distanced themselves from his irrational-bourgeois approach (due to the stigmatization of Korsch and Lukács).
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