title: Benzoylated uronic acid building blocks and synthesis of N-uronate conjugates of lamotrigine.
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 CdCO(3) 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.
authors.affiliation: Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Aslan M
authors.initials: AM
authors.lastname: Esmurziev
authors.forename: Arne
authors.initials: A
authors.lastname: Reimers
authors.forename: Trygve
authors.initials: T
authors.lastname: Andreassen
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Simic
authors.forename: Eirik
authors.initials: E
authors.lastname: Sundby
authors.forename: Bård Helge
authors.initials: BH
authors.lastname: Hoff
mesh_terms: D001554:Benzene / Q000737:chemistry*; D002175:Candida / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism; D000077213:Lamotrigine; D009682:Magnetic Resonance Spectroscopy; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry; D014574:Uronic Acids / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D014227:Triazines; D014574:Uronic Acids; C074259:lamotrigine 2-N-glucuronide; D000431:Ethanol; D001554:Benzene; D000077213:Lamotrigine