1401914-70-2Relevant articles and documents
Scalable syntheses of both enantiomers of DNJNAc and DGJNAc from glucuronolactone: The effect of N-alkylation on hexosaminidase inhibition
Glawar, Andreas F. G.,Best, Daniel,Ayers, Benjamin J.,Miyauchi, Saori,Nakagawa, Shinpei,Aguilar-Moncayo, Matilde,García Fernández, José M.,Ortiz Mellet, Carmen,Crabtree, Elizabeth V.,Butters, Terry D.,Wilson, Francis X.,Kato, Atsushi,Fleet, George W. J.
, p. 9341 - 9359 (2012/09/22)
The efficient scalable syntheses of 2-acetamido-1,2-dideoxy-D-galacto- nojirimycin (DGJNAc) and 2-acetamido-1,2-dideoxy-D-gluco-nojirimycin (DNJNAc) from D-glucuronolactone, as well as of their enantiomers from L-glucuronolactone, are reported. The evaluation of both enantiomers of DNJNAc and DGJNAc, along with their N-alkyl derivatives, as glycosidase inhibitors showed that DGJNAc and its N-alkyl derivatives were all inhibitors of α-GalNAcase but that none of the epimeric DNJNAc derivatives inhibited this enzyme. In contrast, both DGJNAc and DNJNAc, as well as their alkyl derivatives, were potent inhibitors of β-GlcNAcases and β-GalNAcases. Neither of the L-enantiomers showed any significant inhibition of any of the enzymes tested. Correlation of the in vitro inhibition with the cellular data, by using a free oligosaccharide analysis of the lysosomal enzyme inhibition, revealed the following structure-property relationship: hydrophobic side-chains preferentially promoted the intracellular access of iminosugars to those inhibitors with more-hydrophilic side-chain characteristics. Getting the NAc of it: Scalable syntheses of DGJNAc and DNJNAc from D-glucuronolactone are reported. DGJNAc and its N-alkyl derivatives were inhibitors of α-GalNAcase and both DGJNAc and DNJNAc were potent inhibitors of β-GlcNAcases and β-GalNAcases. Copyright
