Evaluation of C-(β-D-galactosyl) and C-(2-deoxy-D-lyxo-hex-1-enopyranosyl) (D-galactal type) derivatives as inhibitors of β-D-galactosidase from Escherichia coli

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Abstract

C-(2-Deoxy-D-lyxo-hex-1-enopyranosyl)formamide was prepared from acetylated C-(β-D-galactopyranosyl)formamide by a radical-mediated bromination-zinc/N-methylimidazole-induced reductive elimination-Zemplen deacetylation reaction sequence. The preparation of acetylated 5-(2-deoxy-D-lyxo-hex-1-enopyranosyl)tetrazole was improved. Methyl C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formimidate was transformed by benzylamine into N-benzyl-C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formamidine and, after hydrolysis to methyl C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formate, into N-benzyl-C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formamide. A series of C-(β-D-galactopyranosyl) and C-(2-deoxy-D-lyxo-hex-1-enopyranosyl) derivatives was comparatively investigated for E. coli β-D-galactosidase inhibitory activity. N-Benzyl-C-(2-deoxy-D-lyxohex-1-enopyranosyl)formamidine was the best inhibitor and had K(i)=6 μM (on the basis of its free base concentration, K(i)=8.3 nM was obtained). Basicity and hydrophobicity of the aglycon proved to be more important factors for the inhibition than the conformation of the sugar ring.

Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalCarbohydrate Research
Volume291
Publication statusPublished - Sep 23 1996

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Galactosidases
Dilatation and Curettage
Escherichia coli
formic acid
Derivatives
Halogenation
Hydrophobicity
Alkalinity
Hydrophobic and Hydrophilic Interactions
Sugars
Conformations
Zinc
Hydrolysis
galactal
formamide
formamidine

Keywords

  • C-glycosides
  • D-galactal derivatives
  • E. coli β-D-galactosidase
  • enzyme inhibition
  • radical-mediated bromination
  • reductive elimination
  • zinc/N-methylimidazole reagent

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry

Cite this

@article{b3b5ff95708948aba0c9f8db78248926,
title = "Evaluation of C-(β-D-galactosyl) and C-(2-deoxy-D-lyxo-hex-1-enopyranosyl) (D-galactal type) derivatives as inhibitors of β-D-galactosidase from Escherichia coli",
abstract = "C-(2-Deoxy-D-lyxo-hex-1-enopyranosyl)formamide was prepared from acetylated C-(β-D-galactopyranosyl)formamide by a radical-mediated bromination-zinc/N-methylimidazole-induced reductive elimination-Zemplen deacetylation reaction sequence. The preparation of acetylated 5-(2-deoxy-D-lyxo-hex-1-enopyranosyl)tetrazole was improved. Methyl C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formimidate was transformed by benzylamine into N-benzyl-C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formamidine and, after hydrolysis to methyl C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formate, into N-benzyl-C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formamide. A series of C-(β-D-galactopyranosyl) and C-(2-deoxy-D-lyxo-hex-1-enopyranosyl) derivatives was comparatively investigated for E. coli β-D-galactosidase inhibitory activity. N-Benzyl-C-(2-deoxy-D-lyxohex-1-enopyranosyl)formamidine was the best inhibitor and had K(i)=6 μM (on the basis of its free base concentration, K(i)=8.3 nM was obtained). Basicity and hydrophobicity of the aglycon proved to be more important factors for the inhibition than the conformation of the sugar ring.",
keywords = "C-glycosides, D-galactal derivatives, E. coli β-D-galactosidase, enzyme inhibition, radical-mediated bromination, reductive elimination, zinc/N-methylimidazole reagent",
author = "L. Kiss and L. Soms{\'a}k",
year = "1996",
month = "9",
day = "23",
language = "English",
volume = "291",
pages = "43--52",
journal = "Carbohydrate Research",
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T1 - Evaluation of C-(β-D-galactosyl) and C-(2-deoxy-D-lyxo-hex-1-enopyranosyl) (D-galactal type) derivatives as inhibitors of β-D-galactosidase from Escherichia coli

AU - Kiss, L.

AU - Somsák, L.

PY - 1996/9/23

Y1 - 1996/9/23

N2 - C-(2-Deoxy-D-lyxo-hex-1-enopyranosyl)formamide was prepared from acetylated C-(β-D-galactopyranosyl)formamide by a radical-mediated bromination-zinc/N-methylimidazole-induced reductive elimination-Zemplen deacetylation reaction sequence. The preparation of acetylated 5-(2-deoxy-D-lyxo-hex-1-enopyranosyl)tetrazole was improved. Methyl C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formimidate was transformed by benzylamine into N-benzyl-C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formamidine and, after hydrolysis to methyl C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formate, into N-benzyl-C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formamide. A series of C-(β-D-galactopyranosyl) and C-(2-deoxy-D-lyxo-hex-1-enopyranosyl) derivatives was comparatively investigated for E. coli β-D-galactosidase inhibitory activity. N-Benzyl-C-(2-deoxy-D-lyxohex-1-enopyranosyl)formamidine was the best inhibitor and had K(i)=6 μM (on the basis of its free base concentration, K(i)=8.3 nM was obtained). Basicity and hydrophobicity of the aglycon proved to be more important factors for the inhibition than the conformation of the sugar ring.

AB - C-(2-Deoxy-D-lyxo-hex-1-enopyranosyl)formamide was prepared from acetylated C-(β-D-galactopyranosyl)formamide by a radical-mediated bromination-zinc/N-methylimidazole-induced reductive elimination-Zemplen deacetylation reaction sequence. The preparation of acetylated 5-(2-deoxy-D-lyxo-hex-1-enopyranosyl)tetrazole was improved. Methyl C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formimidate was transformed by benzylamine into N-benzyl-C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formamidine and, after hydrolysis to methyl C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formate, into N-benzyl-C-(2-deoxy-D-lyxo-hex-1-enopyranosyl)formamide. A series of C-(β-D-galactopyranosyl) and C-(2-deoxy-D-lyxo-hex-1-enopyranosyl) derivatives was comparatively investigated for E. coli β-D-galactosidase inhibitory activity. N-Benzyl-C-(2-deoxy-D-lyxohex-1-enopyranosyl)formamidine was the best inhibitor and had K(i)=6 μM (on the basis of its free base concentration, K(i)=8.3 nM was obtained). Basicity and hydrophobicity of the aglycon proved to be more important factors for the inhibition than the conformation of the sugar ring.

KW - C-glycosides

KW - D-galactal derivatives

KW - E. coli β-D-galactosidase

KW - enzyme inhibition

KW - radical-mediated bromination

KW - reductive elimination

KW - zinc/N-methylimidazole reagent

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VL - 291

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JO - Carbohydrate Research

JF - Carbohydrate Research

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