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.

@article{Crabtree2014SynthesisOT,
  title={Synthesis of the enantiomers of XYLNAc and LYXNAc: comparison of $\beta$-N-acetylhexosaminidase inhibition by the 8 stereoisomers of 2-N-acetylamino-1,2,4-trideoxy-1,4-iminopentitols.},
  author={E. Crabtree and R. Mart{\'i}nez and S. Nakagawa and I. Adachi and T. Butters and A. Kato and G. Fleet and A. F. G. Glawar},
  journal={Organic \& biomolecular chemistry},
  year={2014},
  volume={12 23},
  pages={
          3932-43
        }
}
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… Expand
18 Citations
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References

SHOWING 1-10 OF 60 REFERENCES
Efficient synthesis from d-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-l-arabinitol LABNAc, a potent pyrrolidine inhibitor of hexosaminidases
The synthesis from d-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-l-arabinitol LABNAc proceeded in an overall yield of 25%; the enantiomer, 2-acetamido-1,4-imino-1,2,4-trideoxy-d-arabinitolExpand
Potential glycosidase inhibitors: Synthesis of 1,4-dideoxy-1,4-imino derivatives of D-glucitol, D- and L-xylitol, D- and L-allitol, D- and L-talitol, and D-gulitol
Conversion of 2,3,5,6-tetra-O-benzyl-D-galactofuranose (19) into its oxime and subsequent treatment with methanesulphonyl chloride gave 2,3,5,6-tetra-O-benzyl-4-O-methylsulphonyl-D-galactonitrileExpand
Potent competitive inhibition of α-galactosidase and α-glucosidase activity by 1,4-dideoxy-1,4-iminopentitols: syntheses of 1,4-dideoxy-1,4-imino-d-lyxitol and of both enantiomers of 1,4-dideoxy-1,4-iminoarabinitol
Abstract The syntheses of 1,4-dideoxy-1,4-imino-D-lyxitol (3), 1,4-dideoxy-1,4-imino- d -arabinitol (4) and 1,4-dideoxy-1,4-imino- l -arabinitol (5) are reported; (3) is a potent competitiveExpand
Scalable syntheses of both enantiomers of DNJNAc and DGJNAc from glucuronolactone: the effect of N-alkylation on hexosaminidase inhibition.
TLDR
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. Expand
Synthesis of (2R,3S,4R)-3,4-dihydroxyproline from D-ribonolactone; an approach to the synthesis of polyfunctionalised D-amino acids from sugar lactones. X-Ray molecular structures of 2-azido-3,4-O-(R)-benzylidene-2-deoxy-D-ribono-1,5-lactone, 2-azido-2-deoxy-D-ribono-1,4-lactone, and (2R,3S,3R)-3,4-
A general approach to the synthesis of polyfunctionalised amino acids from sugar lactones, in which nucleophilic displacement by azide ion of O-trifluoromethanesulphonyl esters adjacent to theExpand
An approach to 8 stereoisomers of homonojirimycin from (D)-glucose via kinetic & thermodynamic azido-γ-lactones.
TLDR
Two epimeric azido-heptitols allow biotechnological transformations via Izumoring techniques to 8 of the 16 possible homonojirimycin analogues, 5 of which were isolated pure because of the lack of stereoselectivity of the final reductive amination. Expand
Nitrogen-in-the-ring pyranoses and furanoses: structural basis of inhibition of mammalian glycosidases.
TLDR
Investigation of the contribution of epimerization, deoxygenation, and conformation to the potency of inhibition and specificity of mammalian glycosidases suggests that it superimposes well on the various glycosyl cations. Expand
Polyhydroxylated pyrrolidines from sugar lactomes: Synthesis of 1,4-dideoxy-1,4-imino-d-glucitol from d-galactonolactone and syntheses of 1,4-dideoxy-1,4-imino-d-allitol, 1,4-dideoxy-1,4-imino-d-ribitol, and (2s,3r,4s)-3,4-dihydroxyproline from d-gulonolactone
Abstract The use of readily available sugar lactones in the synthesis of polyhydroxylated pyrrolidines is illustrated by the preparation of the glucosidase inhibitor 1,4-dideoxy-1, 4-imino-D-glucitolExpand
Intermediates for incorporation of tetrahydroxypipecolic acid analogues of α- and β-d-mannopyranose into combinatorial libraries: unexpected nanomolar-range hexosaminidase inhibitors. Synthesis of α- and β-homomannojirimycin
Abstract Homoazasugars have the distinction as a class of natural products in that most of them have been synthesised before they were isolated. Syntheses of α- 1 and β-homomannojirimycin 2 rely onExpand
Looking glass inhibitors: synthesis of a potent naringinase inhibitor l-DIM [1,4-dideoxy-1,4-imino-l-mannitol], the enantiomer of DIM [1,4-dideoxy-1,4-imino-d-mannitol] a potent α-d-mannosidase inhibitor
Abstract The synthesis of l -DIM [1,4-dideoxy-1,4-imino- l -mannitol] and of 1,4-imino- d - glycero - l - talo -heptitol from d - glycero - d - gulo -heptono-1,4-lactone depends on the use ofExpand
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