title: Synthesis of the enantiomers of XYLNAc and LYXNAc: comparison of β-N-acetylhexosaminidase inhibition by the 8 stereoisomers of 2-N-acetylamino-1,2,4-trideoxy-1,4-iminopentitols.
abstract: The enantiomers of XYLNAc (2-N-acetylamino-1,2,4-trideoxy-1,4-iminoxylitol) are prepared from the enantiomers of glucuronolactone; the synthesis of the enantiomers of LYXNAc (2-N-acetylamino-1,2,4-trideoxy-1,4-iminolyxitol) from an L-arabinono-δ-lactone and a D-ribono-δ-lactone is reported. A comparison is made of the inhibition of β-N-acetylhexosaminidases (HexNAcases) and α-N-acetylgalactosaminidase (α-GalNAcase) by 8 stereoisomeric 2-N-acetylamino-1,2,4-trideoxy-1,4-iminopentitols; their N-benzyl derivatives are better inhibitors than the parent compounds. Both XYLNAc and LABNAc are potent inhibitors against HexNAcases. None of the compounds show any inhibition of α-GalNAcase.
authors.affiliation: Oxford Glycobiology Institute, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Crabtree
authors.forename: R Fernando
authors.initials: RF
authors.lastname: Martínez
authors.forename: Shinpei
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Isao
authors.initials: I
authors.lastname: Adachi
authors.forename: Terry D
authors.initials: TD
authors.lastname: Butters
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: George W J
authors.initials: GW
authors.lastname: Fleet
authors.forename: Andreas F G
authors.initials: AF
authors.lastname: Glawar
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007887:Fabaceae / Q000201:enzymology; D007097:Imines / Q000737:chemistry* / Q000494:pharmacology*; D011759:Pyrrolidines / Q000737:chemistry; D013237:Stereoisomerism; D014993:Xylitol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C000596874:2-N-acetylamino-1,2,4-trideoxy-1,4-iminolyxitol; C000596872:2-N-acetylamino-1,2,4-trideoxy-1,4-iminoxylitol; D004791:Enzyme Inhibitors; D007097:Imines; D011759:Pyrrolidines; D001619:beta-N-Acetylhexosaminidases; D014993:Xylitol