Benzoylated uronic acid building blocks and synthesis of n-uronate conjugates of lamotrigine
(2012) In Molecules 17(1). p.820-835- 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-a-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... (More)
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-a-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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- author
- Esmurziev, Aslan M. ; Reimers, Arne LU ; Andreassen, Trygve ; Simic, Nebojsa ; Sundby, Eirik and Hoff, Bard Helge
- publishing date
- 2012-01
- type
- Contribution to journal
- publication status
- published
- keywords
- Fluorinated carbohydrates, Lamotrigine-N2-glucuronide, Uronic acid building blocks
- in
- Molecules
- volume
- 17
- issue
- 1
- article number
- 17010820
- pages
- 820 - 835
- publisher
- MDPI AG
- external identifiers
-
- pmid:22269868
- scopus:84856149541
- ISSN
- 1420-3049
- DOI
- 10.3390/molecules17010820
- language
- English
- LU publication?
- no
- id
- 1b6eff8a-9180-4b92-8ae9-118b389bc998
- date added to LUP
- 2024-08-31 14:50:42
- date last changed
- 2024-09-02 13:02:08
@article{1b6eff8a-9180-4b92-8ae9-118b389bc998,
abstract = {{<p>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-a-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.</p>}},
author = {{Esmurziev, Aslan M. and Reimers, Arne and Andreassen, Trygve and Simic, Nebojsa and Sundby, Eirik and Hoff, Bard Helge}},
issn = {{1420-3049}},
keywords = {{Fluorinated carbohydrates; Lamotrigine-N2-glucuronide; Uronic acid building blocks}},
language = {{eng}},
number = {{1}},
pages = {{820--835}},
publisher = {{MDPI AG}},
series = {{Molecules}},
title = {{Benzoylated uronic acid building blocks and synthesis of n-uronate conjugates of lamotrigine}},
url = {{http://dx.doi.org/10.3390/molecules17010820}},
doi = {{10.3390/molecules17010820}},
volume = {{17}},
year = {{2012}},
}