A stereoselective and self-promoted glycosylation for the synthesis of various N-glycosides and glycosyl sulfonamides from trichloroacetimidates is presented.
N-Glycosyl N-sulfonyl amides have been synthesized by a selfpromoted glycosylation, i. e. without any catalysts, promotors or additives. When the reactions were carried out at lower temperatures a mixture of N-and O-glycosides were observed, where the latter rearranged to give the β-N-glycosides at elevated temperatures. By this method sulfonylated asparagine derivatives can be selectively β-glycosylated in high yields by trichloroacetimidate glycosyl donors of different reactivity including protected glucosamine derivatives. The chemoselectivity in the glycosylations as well as the rearrangements from O-glycosides to β-N-glycosides gives information of the glycosylation mechanism. This method gives access to glycosyl sulfonyl amides under mild conditions.
The Gram-negative
pathogen Pseudomonas
aeruginosa causes severe infections mainly in immunocompromised
or cystic fibrosis
patients and is able to resist antimicrobial treatments. The extracellular
lectin LecB plays a key role in bacterial adhesion to the host and
biofilm formation. For the inhibition of LecB, we designed and synthesized
a set of fucosyl amides, sulfonamides, and thiourea derivatives. Then,
we analyzed their binding to LecB in competitive and direct binding
assays. We identified β-fucosyl amides as unprecedented high-affinity
ligands in the two-digit nanomolar range. X-ray crystallography of
one α- and one β-anomer of N-fucosyl
amides in complex with LecB revealed the interactions responsible
for the high affinity of the β-anomer at atomic level. Further,
the molecules showed good stability in murine and human blood plasma
and hepatic metabolism, providing a basis for future development into
antibacterial drugs.
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