Glycosidase Inhibition by All 10 Stereoisomeric 2,5-Dideoxy-2,5-iminohexitols Prepared from the Enantiomers of Glucuronolactone

Ayers, Benjamin James; Ngo, Nigel; Jenkinson, Sarah F.; Martínez, R. Fernando; Shimada, Yasuhiro; Adachi, Isao; Weymouth‐Wilson, Alexander C.; Kato, Atsushi; Fleet, George W. J.

doi:10.1021/jo301243s

Cited by 39 publications

(49 citation statements)

References 63 publications

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“…The acetonide 26D which has only C-5 OH unprotected allows introduction of azide with inversion, reduction of the lactone at C6 and inversion of configuration at C3 to afford the azido diol 27L in 70% yield on a multigram scale. 24,45 L-Glucuronolactone acetonide 26L 46,47 was converted to the enantiomer L-XYLNAc 20L by an identical procedure.…”

Section: Synthesis Of Enantiomers Of Xylnac 20mentioning

confidence: 99%

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

et al. 2014

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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.

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Section: Synthesis Of Enantiomers Of Xylnac 20mentioning

confidence: 99%

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

et al. 2014

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“…N-Ethyl and N-propyl derivatives of DMDP did not show such changes in their glycosidase inhibition profile (Asano et al 1995). galacto-DMDP 10 is a potent and specific inhibitor of coffee bean α-galactosidase (IC 50 0.19 μM) (Ayers et al 2012), but had no inhibition of β-galactosidase. The corresponding acetic 11 and propionic 12 acids remain potent inhibitors of α-galactosidase, but showed no significant inhibition of β-galactosidase.…”

Section: Glycosidase Inhibitionmentioning

confidence: 93%

“…Residual signals from the solvents were used as an internal reference, except in the case of deuterium oxide, where acetonitrile was used as the reference. The syntheses of all N-alkyl derivatives were carried out directly from their unprotected parent iminosugars and amino acids as previously prepared: 2,5-dideoxy-2,5-imino-d-mannitol (DMDP) 1 (Best et al 2010), 2,5-dideoxy-2,5-imino-d-mannonic acid [(3S)-3-hydroxy-bulgecinine] 13 (Best et al 2010), and deoxynojirimycin (DNJ) 2 (Best et al 2010) and 2,5-dideoxy-2,5-iminogalactitol (galacto-DMDP) 10 from glucuronolactone (Ayers et al 2012), 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) 7 and trans,trans-dihydroxyproline 16 from diacetone glucose (Fleet and Witty 1990).…”

Section: Methodsmentioning

confidence: 99%

Isolation from Stevia rebaudiana of DMDP acetic acid, a novel iminosugar amino acid: synthesis and glycosidase inhibition profile of glycine and β-alanine pyrrolidine amino acids

Martínez¹,

Jenkinson²,

Nakagawa

et al. 2019

Amino Acids

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DMDP acetic acid [N-carboxymethyl-2,5-dideoxy-2,5-imino-d-mannitol] 5 from Stevia rebaudiana is the first isolated natural amino acid derived from iminosugars bearing an N-alkyl acid side chain; it is clear from GCMS studies that such derivatives with acetic and propionic acids are common in a broad range of plants including mulberry, Baphia, and English bluebells, but that they are very difficult to purify. Reaction of unprotected pyrrolidine iminosugars with aqueous glyoxal gives the corresponding N-acetic acids in very high yield; Michael addition of both pyrrolidine and piperidine iminosugars and that of polyhydroxylated prolines to tert-butyl acrylate give the corresponding N-propionic acids in which the amino group of β-alanine is incorporated into the heterocyclic ring. These easy syntheses allow the identification of this new class of amino acid in plant extracts and provide pure samples for biological evaluation. DMDP N-acetic and propionic acids are potent α-galactosidase inhibitors in contrast to potent β-galactosidase inhibition by DMDP.

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“…Iminosugars characterized by a smaller, five-atom ring system, have been described [90,91]. 2,5-dideoxy-2,5-imino- d -altritol (DIA) inhibited AGAL and stabilized it against thermal denaturation and acted as a chaperone when tested on Fabry R301Q lymphoblasts although at a concentration 20 times higher than the optimal one for DGJ.…”

Section: Future Perspectives For Therapymentioning

confidence: 99%

The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations

Citro

Cammisa

Liguori

et al. 2016

IJMS

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Fabry disease is caused by mutations in the GLA gene and is characterized by a large genotypic and phenotypic spectrum. Missense mutations pose a special problem for graduating diagnosis and choosing a cost-effective therapy. Some mutants retain enzymatic activity, but are less stable than the wild type protein. These mutants can be stabilized by small molecules which are defined as pharmacological chaperones. The first chaperone to reach clinical trial is 1-deoxygalactonojirimycin, but others have been tested in vitro. Residual activity of GLA mutants has been measured in the presence or absence of pharmacological chaperones by several authors. Data obtained from transfected cells correlate with those obtained in cells derived from patients, regardless of whether 1-deoxygalactonojirimycin was present or not. The extent to which missense mutations respond to 1-deoxygalactonojirimycin is variable and a reference table of the results obtained by independent groups that is provided with this paper can facilitate the choice of eligible patients. A review of other pharmacological chaperones is provided as well. Frequent mutations can have residual activity as low as one-fourth of normal enzyme in vitro. The reference table with residual activity of the mutants facilitates the identification of non-pathological variants.

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Glycosidase Inhibition by All 10 Stereoisomeric 2,5-Dideoxy-2,5-iminohexitols Prepared from the Enantiomers of Glucuronolactone

Cited by 39 publications

References 63 publications

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

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

Isolation from Stevia rebaudiana of DMDP acetic acid, a novel iminosugar amino acid: synthesis and glycosidase inhibition profile of glycine and β-alanine pyrrolidine amino acids

The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations

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