Benzoylated uronic acid building blocks and synthesis of N-uronate conjugates of lamotrigine
Esmurziev, Aslan; Reimers, Arne; Andreassen, Trygve; Simic, Nebojsa; Sundby, Eirik; Hoff, Bård Helge
Journal article, Peer reviewed
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Date
2012Metadata
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- Institutt for kjemi [1411]
Abstract
A chemoenzymatic approach towards benzoylated uronic acid building blocks
has been investigated starting with benzoylated hexapyranosides using regioselective
C-6 enzymatic hydrolysis as the key step. Two of the building blocks were reacted
with the antiepileptic drug lamotrigine. Glucuronidation of lamotrigine using
methyl (2,3,4-tri-O-benzoyl-α-D-glycopyranosyl bromide)uronate proceeded to give the
N2-conjugate. However, lamotrigine-N2-glucuronide was most efficiently synthesised
from methyl (2,3,4-tri-O-acetyl-α-D-glucopyranosyl bromide)uronate. Employing
nitromethane as solvent with CdCO3 as a base lamotrigine-N2 glucuronide was prepared in a high yield (41%). Also methyl (2,3-di-O-benzoyl-4-deoxy-4-fluoro-α-D-glucosyl bromide)uronate underwent N-glucuronidation, but the product was unstable, eliminating hydrogen fluoride to give the corresponding enoate conjugate.
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