Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

α-Glycosidase enzymes hydrolyse α-glycosidic linkages and are involved in bodily processes such as the catabolism of glycans, intestinal digestion, and the degradation of glycoproteins. Various types of diseases which are caused by the failure of this enzyme to function properly can be treated through enzyme inhibition. The hydroxyethyl derivative of DNJ (Miglitol) is a clinical drug for the treatment of type 2 diabetes. Although the iminosugar D-deoxynojirimisin (D-DNJ) is an excellent micromolar glycosidase inhibitor, the α-glucosidase inhibition activity of D-DNJ lactone intermediates has yet to be reported. Therefore, the scalable synthesis of the D-DNJ intermediates 1,2-O-isopropylidene-α-D-glucurono-3,6-lactone (2), 1,2-O-isopropylidene-β-L-idurono-3,6-lactone (3) and 5-azido-5-deoxy-1,2-O-isopropylidene-α-D-glucurono-3,6-lactone (4) was carried out using D-glucuronolactone (1) as the starting material based on the method reported by Best et al. 2010 with some modification and subsequently, evaluated for anti-α-glucosidase activity. All products were characterised and identified by HPLC-ELSD, mass spectrometry (DI-ESI-MS) and NMR spectroscopy (via comparison of 1D 1H and 13C data with previously reported values). The inhibitory activity of compounds 1-4 towards α-glucosidase from Saccharomyces cerevisiae was evaluated using the p-nitrophenyl α-D-glucopyranoside substrate. Compound 3 showed 29.5% inhibition followed by 2 (21.4%), 1 (15.8%) and 4 (15.7%) compared to the positive control, quercetin (72.7%).

Type

Journal article

Journal

Journal of Chemical Biology

Publisher

Springer Verlag

Publication Date

16/08/2019