posted on 2024-02-14, 03:06authored byJose L. Gonzalez-Alfonso, Cristina Alonso, Ana Poveda, Zorica Ubiparip, Antonio O. Ballesteros, Tom Desmet, Jesús Jiménez-Barbero, Luisa Coderch, Francisco J. Plou
The acylation of
flavonoids serves as a means to alter
their physicochemical
properties, enhance their stability, and improve their bioactivity.
Compared with natural flavonoid glycosides, the acylation of nonglycosylated
flavonoids presents greater challenges since they contain fewer reactive
sites. In this work, we propose an efficient strategy to solve this
problem based on a first α-glucosylation step catalyzed by a
sucrose phosphorylase, followed by acylation using a lipase. The method
was applied to phloretin, a bioactive dihydrochalcone mainly present
in apples. Phloretin underwent initial glucosylation at the 4′-OH
position, followed by subsequent (and quantitative) acylation with
C8, C12, and C16 acyl chains employing an immobilized lipase from Thermomyces lanuginosus. Electrospray ionization-mass
spectrometry (ESI-MS) and two-dimensional nuclear magnetic resonance
spectroscopy (2D-NMR) confirmed that the acylation took place at 6-OH
of glucose. The water solubility of C8 acyl glucoside closely resembled
that of aglycone, but for C12 and C16 derivatives, it was approximately
3 times lower. Compared with phloretin, the radical scavenging capacity
of the new derivatives slightly decreased with 2,2-diphenyl-1-picrylhydrazyl
(DPPH) and was similar to 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic
acid) (ABTS•+). Interestingly, C12 acyl-α-glucoside
displayed an enhanced (3-fold) transdermal absorption (using pig skin
biopsies) compared to phloretin and its α-glucoside.