Synthesis of Hydrophobic Derivatives of Stilbenes with Improved Permeability and Limited Phase II Reactions

Stilbenes can promote
human health due to their several
bioactivities.
However, their low bioavailability is a limiting factor for the in vivo bioactivity of these plant bioactive compounds.
This low bioavailability has been previously associated with their
rapid absorption and phase II metabolism. In this work, the synthesis
of hydrophobic stilbene derivatives is explored as a promising alternative.
Chemical and enzymatic syntheses were compared, achieving higher efficiency
with the former. The synthesized derivatives were characterized to
ease future research. Hydrophobic resveratrol derivatives improved
the apparent permeability of resveratrol across the Caco-2 intestinal
cells. Moreover, hydrophobic derivatives of resveratrol and oxyresveratrol
showed a lower degree of sulfation and glucuronidation compared to
original stilbenes, which could be an advantage in avoiding phase
II reactions that decrease the bioavailability of stilbenes. These
results support hydrophobic stilbene derivatives as precursors of
natural stilbenes, highlighting their strong potential for oral administration
through functional foods in humans.