Synthesis of 2-(β-d-glucopyranosyl)-5-(substituted-amino)-1,3,4-oxa- and -thiadiazoles for the inhibition of glycogen phosphorylase

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Abstract

O-Perbenzoylated 4-phenyl-[C-(β-d-glucopyranosyl)formaldehyde] semicarbazone was prepared in the reaction of O-perbenzoylated β-d-glucopyranosyl cyanide and 4-phenylsemicarbazide in the presence of Raney-Ni. Acylation of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde semicarbazone furnished the corresponding 4-acyl-[C-(β-d-glucopyranosyl) formaldehyde]semicarbazones. The reaction of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde semicarbazone with the corresponding thiosemicarbazide resulted in O-perbenzoylated C-(β-d-glucopyranosyl) formaldehyde thiosemicarbazone and its 4-phenyl derivative. Acylation of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde thiosemicarbazone provided the corresponding 4-acyl-2-acylamino-5-(β-d-glucopyranosyl)- Δ2-1,3,4-thiadiazolidines. Oxidative transformations of these precursors gave O-protected 2-(β-d-glucopyranosyl)-5-substituted-amino-1,3, 4-oxa- and -thiadiazoles. The O-benzoyl protecting groups were removed under base-catalysed transesterification conditions. The C-glucopyranosyl heterocyclic compounds proved inactive against rabbit muscle glycogen phosphorylase b, however, the semicarbazones showed moderate inhibition (best inhibitor was 4-phenyl-[C-(β-d-glucopyranosyl)formaldehyde]semicarbazone (Ki = 29 μM).

Original languageEnglish
Pages (from-to)187-195
Number of pages9
JournalCarbohydrate Research
Volume381
DOIs
Publication statusPublished - 2013

Fingerprint

Thiadiazoles
Semicarbazones
Glycogen Phosphorylase
Formaldehyde
Thiosemicarbazones
Acylation
Phosphorylase b
Heterocyclic Compounds
Transesterification
Cyanides
1,3,4-thiadiazole
Muscle
Rabbits
Derivatives
Muscles

Keywords

  • C-Glycosyl-1,3,4-oxadiazole
  • C-Glycosyl-1,3,4-thiadiazole
  • C-Glycosyl-formaldehyde (thio)semicarbazone
  • Glycogen phosphorylase
  • Inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Analytical Chemistry
  • Organic Chemistry

Cite this

@article{9e33b5be6e314f98b3c45bcf379290e6,
title = "Synthesis of 2-(β-d-glucopyranosyl)-5-(substituted-amino)-1,3,4-oxa- and -thiadiazoles for the inhibition of glycogen phosphorylase",
abstract = "O-Perbenzoylated 4-phenyl-[C-(β-d-glucopyranosyl)formaldehyde] semicarbazone was prepared in the reaction of O-perbenzoylated β-d-glucopyranosyl cyanide and 4-phenylsemicarbazide in the presence of Raney-Ni. Acylation of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde semicarbazone furnished the corresponding 4-acyl-[C-(β-d-glucopyranosyl) formaldehyde]semicarbazones. The reaction of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde semicarbazone with the corresponding thiosemicarbazide resulted in O-perbenzoylated C-(β-d-glucopyranosyl) formaldehyde thiosemicarbazone and its 4-phenyl derivative. Acylation of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde thiosemicarbazone provided the corresponding 4-acyl-2-acylamino-5-(β-d-glucopyranosyl)- Δ2-1,3,4-thiadiazolidines. Oxidative transformations of these precursors gave O-protected 2-(β-d-glucopyranosyl)-5-substituted-amino-1,3, 4-oxa- and -thiadiazoles. The O-benzoyl protecting groups were removed under base-catalysed transesterification conditions. The C-glucopyranosyl heterocyclic compounds proved inactive against rabbit muscle glycogen phosphorylase b, however, the semicarbazones showed moderate inhibition (best inhibitor was 4-phenyl-[C-(β-d-glucopyranosyl)formaldehyde]semicarbazone (Ki = 29 μM).",
keywords = "C-Glycosyl-1,3,4-oxadiazole, C-Glycosyl-1,3,4-thiadiazole, C-Glycosyl-formaldehyde (thio)semicarbazone, Glycogen phosphorylase, Inhibitor",
author = "B{\'e}la Szocs and M. T{\'o}th and T. Docsa and P. Gergely and L. Soms{\'a}k",
year = "2013",
doi = "10.1016/j.carres.2013.03.009",
language = "English",
volume = "381",
pages = "187--195",
journal = "Carbohydrate Research",
issn = "0008-6215",
publisher = "Elsevier BV",

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TY - JOUR

T1 - Synthesis of 2-(β-d-glucopyranosyl)-5-(substituted-amino)-1,3,4-oxa- and -thiadiazoles for the inhibition of glycogen phosphorylase

AU - Szocs, Béla

AU - Tóth, M.

AU - Docsa, T.

AU - Gergely, P.

AU - Somsák, L.

PY - 2013

Y1 - 2013

N2 - O-Perbenzoylated 4-phenyl-[C-(β-d-glucopyranosyl)formaldehyde] semicarbazone was prepared in the reaction of O-perbenzoylated β-d-glucopyranosyl cyanide and 4-phenylsemicarbazide in the presence of Raney-Ni. Acylation of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde semicarbazone furnished the corresponding 4-acyl-[C-(β-d-glucopyranosyl) formaldehyde]semicarbazones. The reaction of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde semicarbazone with the corresponding thiosemicarbazide resulted in O-perbenzoylated C-(β-d-glucopyranosyl) formaldehyde thiosemicarbazone and its 4-phenyl derivative. Acylation of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde thiosemicarbazone provided the corresponding 4-acyl-2-acylamino-5-(β-d-glucopyranosyl)- Δ2-1,3,4-thiadiazolidines. Oxidative transformations of these precursors gave O-protected 2-(β-d-glucopyranosyl)-5-substituted-amino-1,3, 4-oxa- and -thiadiazoles. The O-benzoyl protecting groups were removed under base-catalysed transesterification conditions. The C-glucopyranosyl heterocyclic compounds proved inactive against rabbit muscle glycogen phosphorylase b, however, the semicarbazones showed moderate inhibition (best inhibitor was 4-phenyl-[C-(β-d-glucopyranosyl)formaldehyde]semicarbazone (Ki = 29 μM).

AB - O-Perbenzoylated 4-phenyl-[C-(β-d-glucopyranosyl)formaldehyde] semicarbazone was prepared in the reaction of O-perbenzoylated β-d-glucopyranosyl cyanide and 4-phenylsemicarbazide in the presence of Raney-Ni. Acylation of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde semicarbazone furnished the corresponding 4-acyl-[C-(β-d-glucopyranosyl) formaldehyde]semicarbazones. The reaction of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde semicarbazone with the corresponding thiosemicarbazide resulted in O-perbenzoylated C-(β-d-glucopyranosyl) formaldehyde thiosemicarbazone and its 4-phenyl derivative. Acylation of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde thiosemicarbazone provided the corresponding 4-acyl-2-acylamino-5-(β-d-glucopyranosyl)- Δ2-1,3,4-thiadiazolidines. Oxidative transformations of these precursors gave O-protected 2-(β-d-glucopyranosyl)-5-substituted-amino-1,3, 4-oxa- and -thiadiazoles. The O-benzoyl protecting groups were removed under base-catalysed transesterification conditions. The C-glucopyranosyl heterocyclic compounds proved inactive against rabbit muscle glycogen phosphorylase b, however, the semicarbazones showed moderate inhibition (best inhibitor was 4-phenyl-[C-(β-d-glucopyranosyl)formaldehyde]semicarbazone (Ki = 29 μM).

KW - C-Glycosyl-1,3,4-oxadiazole

KW - C-Glycosyl-1,3,4-thiadiazole

KW - C-Glycosyl-formaldehyde (thio)semicarbazone

KW - Glycogen phosphorylase

KW - Inhibitor

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U2 - 10.1016/j.carres.2013.03.009

DO - 10.1016/j.carres.2013.03.009

M3 - Article

C2 - 23582340

AN - SCOPUS:84886729376

VL - 381

SP - 187

EP - 195

JO - Carbohydrate Research

JF - Carbohydrate Research

SN - 0008-6215

ER -