Glycoamphiphiles have attracted considerable interest
in a broad
range of application fields owing to their solution and bulk-state
self-assembly abilities. Despite their importance, the straightforward
synthesis of glycoamphiphiles consisting of a hydrophilic carbohydrate
linked to a hydrophobic aglycone remains one of the major challenges
in glycosciences. Here, a rapid, simple, and efficient synthetic access
to chemically stable glycoamphiphiles at physiological pH, namely, N-(β-d-glycosyl)-2-alkylbenzamide, is reported.
It leverages the nonreductive amination of unprotected carbohydrates
with ortho-substituted aniline derivatives which
could be readily obtained by reacting commercially available primary
alkylamines with isatoic anhydride. This strategy avoids protection
and deprotection of sugar hydroxyl groups and the use of reductive
agents, which makes it advantageous in terms of atom and step economy.
Moreover, in order to circumvent the cons of classical N-aryl glycosylation, we investigate the use of microwave as a heat
source that provides fast, clean, and high-yield β-N-arylation of unprotected carbohydrates. Their self-assembly into
water led to multiple morphologies of dynamic supramolecular glycoamphiphiles
that were characterized to assess their ability to bind to lectins
from pathogenic bacteria. Biophysical interactions probed by isothermal
titration microcalorimetry revealed micromolar affinities for most
of the synthesized glycoamphiphiles.