Two isosteric fluorinated derivatives of the powerful
                glucosidase inhibitors1-deoxynojirimycin and
                2,5-dideoxy-2,5-imino-D-mannitol: Syntheses and
                glycosidase-inhibitory activities of
                1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol and of
                1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol

Søren Møller Andersen; Michael Ebner; Christian W. Ekhart; Günther Gradnig; Günther Legler; Inge Lundt; A.E. Stütz; S.G. Withers; T. Wrodnigg

Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol: Syntheses and glycosidase-inhibitory activities of 1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol and of 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol

Søren Møller Andersen, Michael Ebner, Christian W. Ekhart, Günther Gradnig, Günther Legler, Inge Lundt, A.E. Stütz, S.G. Withers, T. Wrodnigg

Research output: Contribution to journal › Journal article › Research

Abstract

1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol, the 2-deoxyfluoro derivative of 1-deoxynojirimycin, as well as 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol and 2,5-dideoxy-2,5-imino-1-O-methyl-D-mannitol, two new analogues of the natural product and powerful glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol, were synthesised featuring glucose isomerase-catalysed aldose-ketose interconvertion reactions as the key steps of the syntheses.Results of inhibition studies conducted with these compounds and previously obtained deoxyfluoro derivatives of 1-deoxynojirimycin, employing glucosidases from various sources, showed that the replacement of a hydroxyl function by fluorine caused an impairment of the inhibitory potency. This effect was smallest for the hydroxyl group at C-6 and up to four orders of magnitude larger for replacements at C-2 and C-3.

Original language	English
Journal	Carbohydrate Research 301
Pages (from-to)	155-166
Publication status	Published - 1997

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Andersen, S. M., Ebner, M., Ekhart, C. W., Gradnig, G., Legler, G., Lundt, I., Stütz, A. E., Withers, S. G., & Wrodnigg, T. (1997). Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol: Syntheses and glycosidase-inhibitory activities of 1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol and of 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol. Carbohydrate Research 301, 155-166.

Andersen, Søren Møller ; Ebner, Michael ; Ekhart, Christian W. et al. / Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol: Syntheses and glycosidase-inhibitory activities of 1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol and of 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol. In: Carbohydrate Research 301. 1997 ; pp. 155-166.

@article{204c37ee24ef40ec84cd095cc9ef6e7a,

title = "Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol: Syntheses and glycosidase-inhibitory activities of 1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol and of 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol",

abstract = "1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol, the 2-deoxyfluoro derivative of 1-deoxynojirimycin, as well as 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol and 2,5-dideoxy-2,5-imino-1-O-methyl-D-mannitol, two new analogues of the natural product and powerful glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol, were synthesised featuring glucose isomerase-catalysed aldose-ketose interconvertion reactions as the key steps of the syntheses.Results of inhibition studies conducted with these compounds and previously obtained deoxyfluoro derivatives of 1-deoxynojirimycin, employing glucosidases from various sources, showed that the replacement of a hydroxyl function by fluorine caused an impairment of the inhibitory potency. This effect was smallest for the hydroxyl group at C-6 and up to four orders of magnitude larger for replacements at C-2 and C-3.",

author = "Andersen, {S{\o}ren M{\o}ller} and Michael Ebner and Ekhart, {Christian W.} and G{\"u}nther Gradnig and G{\"u}nther Legler and Inge Lundt and A.E. St{\"u}tz and S.G. Withers and T. Wrodnigg",

year = "1997",

language = "English",

pages = "155--166",

journal = "Carbohydrate Research 301",

issn = "1873-426X",

publisher = "Pergamon Press",

}

Andersen, SM, Ebner, M, Ekhart, CW, Gradnig, G, Legler, G, Lundt, I, Stütz, AE, Withers, SG & Wrodnigg, T 1997, 'Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol: Syntheses and glycosidase-inhibitory activities of 1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol and of 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol', Carbohydrate Research 301, pp. 155-166.

Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol: Syntheses and glycosidase-inhibitory activities of 1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol and of 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol. / Andersen, Søren Møller; Ebner, Michael; Ekhart, Christian W. et al.
In: Carbohydrate Research 301, 1997, p. 155-166.

Research output: Contribution to journal › Journal article › Research

TY - JOUR

T1 - Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol: Syntheses and glycosidase-inhibitory activities of 1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol and of 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol

AU - Andersen, Søren Møller

AU - Ebner, Michael

AU - Ekhart, Christian W.

AU - Gradnig, Günther

AU - Legler, Günther

AU - Lundt, Inge

AU - Stütz, A.E.

AU - Withers, S.G.

AU - Wrodnigg, T.

PY - 1997

Y1 - 1997

N2 - 1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol, the 2-deoxyfluoro derivative of 1-deoxynojirimycin, as well as 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol and 2,5-dideoxy-2,5-imino-1-O-methyl-D-mannitol, two new analogues of the natural product and powerful glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol, were synthesised featuring glucose isomerase-catalysed aldose-ketose interconvertion reactions as the key steps of the syntheses.Results of inhibition studies conducted with these compounds and previously obtained deoxyfluoro derivatives of 1-deoxynojirimycin, employing glucosidases from various sources, showed that the replacement of a hydroxyl function by fluorine caused an impairment of the inhibitory potency. This effect was smallest for the hydroxyl group at C-6 and up to four orders of magnitude larger for replacements at C-2 and C-3.

AB - 1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol, the 2-deoxyfluoro derivative of 1-deoxynojirimycin, as well as 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol and 2,5-dideoxy-2,5-imino-1-O-methyl-D-mannitol, two new analogues of the natural product and powerful glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol, were synthesised featuring glucose isomerase-catalysed aldose-ketose interconvertion reactions as the key steps of the syntheses.Results of inhibition studies conducted with these compounds and previously obtained deoxyfluoro derivatives of 1-deoxynojirimycin, employing glucosidases from various sources, showed that the replacement of a hydroxyl function by fluorine caused an impairment of the inhibitory potency. This effect was smallest for the hydroxyl group at C-6 and up to four orders of magnitude larger for replacements at C-2 and C-3.

M3 - Journal article

SN - 1873-426X

SP - 155

EP - 166

JO - Carbohydrate Research 301

JF - Carbohydrate Research 301

ER -

Andersen SM, Ebner M, Ekhart CW, Gradnig G, Legler G, Lundt I et al. Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol: Syntheses and glycosidase-inhibitory activities of 1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol and of 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol. Carbohydrate Research 301. 1997;155-166.