| dc.description.abstract | The enzymatic hydrolysis of the benzoylated methyl pyranosides has been investigated using Candida rugosa lipase (CRL) as a catalyst. Hydrolyses of all substrates proceeded in a regiospecific manner at C-6. No acyl migration was observed for all hydrolysed products. The hydrolysis has been optimised with special focus on the effect of co-solvent, temperature and reaction components. Preparative useful reactions were identified for hydrolyses of methyl 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranoside (1a), methyl 2,3,4,6-tetra-O-benzoyl- α-D-galactopyranoside (2a), methyl 2,3,4,6-tetra- O-benzoyl-ß-D-galactopyranoside (5a), methyl 2,3,6-tri-O-benzoyl-α-Dgalactopyranoside (6a) and methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-fluoro-α-Dglucopyranoside (7a). For hydrolyses of the methyl 2,3,4,6-tetra-O-benzoyl-α-Dmannopyranoside (3a) and methyl 2,3,4,6-tetra-O-benzoyl-ß-D-glucopyranoside (4a) low yields were experienced (<10%).
DAST and bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-FluorTM) have been employed in the fluorination of the benzoylated and non-benzoylated methyl pyranosides. Their reactivity was evaluated, eight new fluorinated carbohydrates were prepared and characterised by high-field NMR spectroscopy. Performed investigations demonstrated Deoxo-FluorTM as a good and safer alternative to the DAST. The use of Deoxo-FluorTM found to be especially useful in the preparation of C-6 fluorinated methyl 2,3,4-tri-O-benzoyl-6-deoxy-6-fluoro-ß-D-glucopyranoside (4c), avoiding a regioselective C1→C6 migration of the anomeric methoxy group experienced with DAST-mediated fluorination. In the fluorination of unprotected methyl α-Dmannopyranoside (23a), the methyl 4,6-dideoxy-4,6-difluoro-α-D-talopyranoside 2,3- cyclic sulfite (3e) was isolated using both fluorinating agents.
The chemical synthesis of the main metabolite of antiepileptic drug Lamotrigine, Lamotrigine-N2-glucuronide, has been developed using commercially available methyl (2,3,4-tri-O-acetyl-α-D-glucopyranosyl bromide) uronate (12a) as a glycosyl donor. Characterization and full 1H and 13C NMR assignments of the synthesised LTG-N2-glucuronide (13a) have been performed by extensive NMRexperiments. As alternatives to the glycosyl bromide 12a, fluorinated and non fluorinated benzoyl uronic acid derivatives have been prepared. Their usefulness in the glycosylation with Lamotrigine has been investigated. Glycosylation of Lamotrigine using the methyl (2,3,4-tri-O-benzoyl-α-D-glucopyranosyl bromide) uronate (14c) gave the desired Lamotrigine-N2-glycoside 20a in moderate yield. However, methyl (2,3-di- O-benzoyl-4-deoxy-4-fluoro-α-D-glucopyranosyl bromide) uronate (16c) proved to be unstable under refluxing conditions, and along with expected fluorinated Lamotrigine- N2-glycoside 18a, the elimination of the fluorine was obtained. Finally, a number of benzoylated carbohydrate derivatives have been characterised by NMR spectroscopy | nb_NO |
