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.
Keywords: uronic acid building blocks; lamotrigine-N2-glucuronide; fluorinated carbohydrates
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Esmurziev, A.M.; Reimers, A.; Andreassen, T.; Simic, N.; Sundby, E.; Hoff, B.H. Benzoylated Uronic Acid Building Blocks and Synthesis of N-Uronate Conjugates of Lamotrigine. Molecules 2012, 17, 820-835.
Esmurziev AM, Reimers A, Andreassen T, Simic N, Sundby E, Hoff BH. Benzoylated Uronic Acid Building Blocks and Synthesis of N-Uronate Conjugates of Lamotrigine. Molecules. 2012; 17(1):820-835.
Esmurziev, Aslan M.; Reimers, Arne; Andreassen, Trygve; Simic, Nebojsa; Sundby, Eirik; Hoff, Bård Helge. 2012. "Benzoylated Uronic Acid Building Blocks and Synthesis of N-Uronate Conjugates of Lamotrigine." Molecules 17, no. 1: 820-835.