Synthesis of variously coupled conjugates of d-glucose, 1,3,4-oxadiazole, and 1,2,3-triazole for inhibition of glycogen phosphorylase

Sándor Kun, Gerg Z. Nagy, M. Tóth, Laura Czecze, Albert Nguyen Van Nhien, T. Docsa, P. Gergely, Maria Despoina Charavgi, Paraskevi V. Skourti, Evangelia D. Chrysina, T. Patonay, L. Somsák

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

5-(O-Perbenzoylated-β-d-glucopyranosyl)tetrazole was obtained from O-perbenzoylated-β-d-glucopyranosyl cyanide by Bu3SnN 3 or Me3SiN3-Bu2SnO. This tetrazole was transformed into 5-ethynyl- as well as 5-chloromethyl-2-(O-perbenzoylated- β-d-glucopyranosyl)-1,3,4-oxadiazoles by acylation with propiolic acid-DCC or chloroacetyl chloride, respectively. The chloromethyl oxadiazole gave the corresponding azidomethyl derivative on treatment with NaN3. These compounds were reacted with several alkynes and azides under Cu(I) catalysed cycloaddition conditions to give, after removal of the protecting groups by the Zemplén protocol, β-d-glucopyranosyl-1,3,4-oxadiazolyl-1,2,3- triazole, β-d-glucopyranosyl-1,2,3-triazolyl-1,3,4-oxadiazole, and β-d-glucopyranosyl-1,3,4-oxadiazolylmethyl-1,2,3-triazole type compounds. 5-Phenyltetrazole was also transformed under the above conditions into a series of aryl-1,3,4-oxadiazolyl-1,2,3-triazoles, aryl-1,2,3-triazolyl-1,3,4- oxadiazoles, and aryl-1,3,4-oxadiazolylmethyl-1,2,3-triazoles. The new compounds were assayed against rabbit muscle glycogen phosphorylase b and the best inhibitors had inhibition constants in the upper micromolar range (2-phenyl-5-[1-(β-d-glucopyranosyl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 36: Ki = 854 μM, 2-(β-d-glucopyranosyl)-5-[1-(naphthalen-2- yl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 47: Ki = 745 μM).

Original languageEnglish
Pages (from-to)1427-1438
Number of pages12
JournalCarbohydrate Research
Volume346
Issue number12
DOIs
Publication statusPublished - Sep 6 2011

Fingerprint

Glycogen Phosphorylase
Triazoles
Glucose
Phosphorylase b
Oxadiazoles
Acylation
Sodium Azide
Alkynes
Azides
Cycloaddition
Cycloaddition Reaction
Cyanides
Muscle
1,3,4-oxadiazole
Rabbits
Derivatives
Muscles

Keywords

  • β-d-Glucopyranosyl derivatives
  • 1,2,3-Triazole
  • 1,3,4-Oxadiazole
  • Azide-alkyne cycloaddition
  • Glycogen phosphorylase inhibitor
  • Tetrazole

ASJC Scopus subject areas

  • Biochemistry
  • Analytical Chemistry
  • Organic Chemistry

Cite this

Synthesis of variously coupled conjugates of d-glucose, 1,3,4-oxadiazole, and 1,2,3-triazole for inhibition of glycogen phosphorylase. / Kun, Sándor; Nagy, Gerg Z.; Tóth, M.; Czecze, Laura; Van Nhien, Albert Nguyen; Docsa, T.; Gergely, P.; Charavgi, Maria Despoina; Skourti, Paraskevi V.; Chrysina, Evangelia D.; Patonay, T.; Somsák, L.

In: Carbohydrate Research, Vol. 346, No. 12, 06.09.2011, p. 1427-1438.

Research output: Contribution to journalArticle

Kun, Sándor ; Nagy, Gerg Z. ; Tóth, M. ; Czecze, Laura ; Van Nhien, Albert Nguyen ; Docsa, T. ; Gergely, P. ; Charavgi, Maria Despoina ; Skourti, Paraskevi V. ; Chrysina, Evangelia D. ; Patonay, T. ; Somsák, L. / Synthesis of variously coupled conjugates of d-glucose, 1,3,4-oxadiazole, and 1,2,3-triazole for inhibition of glycogen phosphorylase. In: Carbohydrate Research. 2011 ; Vol. 346, No. 12. pp. 1427-1438.
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abstract = "5-(O-Perbenzoylated-β-d-glucopyranosyl)tetrazole was obtained from O-perbenzoylated-β-d-glucopyranosyl cyanide by Bu3SnN 3 or Me3SiN3-Bu2SnO. This tetrazole was transformed into 5-ethynyl- as well as 5-chloromethyl-2-(O-perbenzoylated- β-d-glucopyranosyl)-1,3,4-oxadiazoles by acylation with propiolic acid-DCC or chloroacetyl chloride, respectively. The chloromethyl oxadiazole gave the corresponding azidomethyl derivative on treatment with NaN3. These compounds were reacted with several alkynes and azides under Cu(I) catalysed cycloaddition conditions to give, after removal of the protecting groups by the Zempl{\'e}n protocol, β-d-glucopyranosyl-1,3,4-oxadiazolyl-1,2,3- triazole, β-d-glucopyranosyl-1,2,3-triazolyl-1,3,4-oxadiazole, and β-d-glucopyranosyl-1,3,4-oxadiazolylmethyl-1,2,3-triazole type compounds. 5-Phenyltetrazole was also transformed under the above conditions into a series of aryl-1,3,4-oxadiazolyl-1,2,3-triazoles, aryl-1,2,3-triazolyl-1,3,4- oxadiazoles, and aryl-1,3,4-oxadiazolylmethyl-1,2,3-triazoles. The new compounds were assayed against rabbit muscle glycogen phosphorylase b and the best inhibitors had inhibition constants in the upper micromolar range (2-phenyl-5-[1-(β-d-glucopyranosyl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 36: Ki = 854 μM, 2-(β-d-glucopyranosyl)-5-[1-(naphthalen-2- yl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 47: Ki = 745 μM).",
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T1 - Synthesis of variously coupled conjugates of d-glucose, 1,3,4-oxadiazole, and 1,2,3-triazole for inhibition of glycogen phosphorylase

AU - Kun, Sándor

AU - Nagy, Gerg Z.

AU - Tóth, M.

AU - Czecze, Laura

AU - Van Nhien, Albert Nguyen

AU - Docsa, T.

AU - Gergely, P.

AU - Charavgi, Maria Despoina

AU - Skourti, Paraskevi V.

AU - Chrysina, Evangelia D.

AU - Patonay, T.

AU - Somsák, L.

PY - 2011/9/6

Y1 - 2011/9/6

N2 - 5-(O-Perbenzoylated-β-d-glucopyranosyl)tetrazole was obtained from O-perbenzoylated-β-d-glucopyranosyl cyanide by Bu3SnN 3 or Me3SiN3-Bu2SnO. This tetrazole was transformed into 5-ethynyl- as well as 5-chloromethyl-2-(O-perbenzoylated- β-d-glucopyranosyl)-1,3,4-oxadiazoles by acylation with propiolic acid-DCC or chloroacetyl chloride, respectively. The chloromethyl oxadiazole gave the corresponding azidomethyl derivative on treatment with NaN3. These compounds were reacted with several alkynes and azides under Cu(I) catalysed cycloaddition conditions to give, after removal of the protecting groups by the Zemplén protocol, β-d-glucopyranosyl-1,3,4-oxadiazolyl-1,2,3- triazole, β-d-glucopyranosyl-1,2,3-triazolyl-1,3,4-oxadiazole, and β-d-glucopyranosyl-1,3,4-oxadiazolylmethyl-1,2,3-triazole type compounds. 5-Phenyltetrazole was also transformed under the above conditions into a series of aryl-1,3,4-oxadiazolyl-1,2,3-triazoles, aryl-1,2,3-triazolyl-1,3,4- oxadiazoles, and aryl-1,3,4-oxadiazolylmethyl-1,2,3-triazoles. The new compounds were assayed against rabbit muscle glycogen phosphorylase b and the best inhibitors had inhibition constants in the upper micromolar range (2-phenyl-5-[1-(β-d-glucopyranosyl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 36: Ki = 854 μM, 2-(β-d-glucopyranosyl)-5-[1-(naphthalen-2- yl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 47: Ki = 745 μM).

AB - 5-(O-Perbenzoylated-β-d-glucopyranosyl)tetrazole was obtained from O-perbenzoylated-β-d-glucopyranosyl cyanide by Bu3SnN 3 or Me3SiN3-Bu2SnO. This tetrazole was transformed into 5-ethynyl- as well as 5-chloromethyl-2-(O-perbenzoylated- β-d-glucopyranosyl)-1,3,4-oxadiazoles by acylation with propiolic acid-DCC or chloroacetyl chloride, respectively. The chloromethyl oxadiazole gave the corresponding azidomethyl derivative on treatment with NaN3. These compounds were reacted with several alkynes and azides under Cu(I) catalysed cycloaddition conditions to give, after removal of the protecting groups by the Zemplén protocol, β-d-glucopyranosyl-1,3,4-oxadiazolyl-1,2,3- triazole, β-d-glucopyranosyl-1,2,3-triazolyl-1,3,4-oxadiazole, and β-d-glucopyranosyl-1,3,4-oxadiazolylmethyl-1,2,3-triazole type compounds. 5-Phenyltetrazole was also transformed under the above conditions into a series of aryl-1,3,4-oxadiazolyl-1,2,3-triazoles, aryl-1,2,3-triazolyl-1,3,4- oxadiazoles, and aryl-1,3,4-oxadiazolylmethyl-1,2,3-triazoles. The new compounds were assayed against rabbit muscle glycogen phosphorylase b and the best inhibitors had inhibition constants in the upper micromolar range (2-phenyl-5-[1-(β-d-glucopyranosyl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 36: Ki = 854 μM, 2-(β-d-glucopyranosyl)-5-[1-(naphthalen-2- yl)-1,2,3-triazol-4-yl]-1,3,4-oxadiazole 47: Ki = 745 μM).

KW - β-d-Glucopyranosyl derivatives

KW - 1,2,3-Triazole

KW - 1,3,4-Oxadiazole

KW - Azide-alkyne cycloaddition

KW - Glycogen phosphorylase inhibitor

KW - Tetrazole

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DO - 10.1016/j.carres.2011.03.004

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