Synthesis of a C-glucosylated cyclopropylamide and evaluation as a glycogen phosphorylase inhibitor

Philippe Bertus, Jan Szymoniak, Erwann Jeanneau, T. Docsa, P. Gergely, Jean Pierre Praly, Sébastien Vidal

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The synthesis of carbohydrate-based glycogen phosphorylase inhibitors is attractive for potential applications in the treatment of type 2 diabetes. A titanium-mediated synthesis led to a benzoylated C-glucosylated cyclopropylamine intermediate, which underwent a benzoyl migration to afford the corresponding 2-hydroxy-C-glycoside. X-ray crystallographic studies revealed a unit cell composed of four molecules as pairs of dimers connected through two hydrogen bonds. The deprotection of the benzoate esters under Zemplén conditions afforded a glycogen phosphorylase inhibitor candidate displaying weak inhibition toward glycogen phosphorylase (16% at 2.5 mM).

Original languageEnglish
Pages (from-to)4774-4778
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number17
DOIs
Publication statusPublished - Sep 1 2008

Fingerprint

Glycogen Phosphorylase
Benzoates
Medical problems
Titanium
Dimers
Type 2 Diabetes Mellitus
Hydrogen
Hydrogen bonds
Esters
Carbohydrates
X-Rays
X rays
Molecules

Keywords

  • Acyl migration
  • C-Glycoside
  • Cyclopropane
  • Glycogen phosphorylase
  • Nitrile
  • Titanium

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Synthesis of a C-glucosylated cyclopropylamide and evaluation as a glycogen phosphorylase inhibitor. / Bertus, Philippe; Szymoniak, Jan; Jeanneau, Erwann; Docsa, T.; Gergely, P.; Praly, Jean Pierre; Vidal, Sébastien.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 17, 01.09.2008, p. 4774-4778.

Research output: Contribution to journalArticle

Bertus, Philippe ; Szymoniak, Jan ; Jeanneau, Erwann ; Docsa, T. ; Gergely, P. ; Praly, Jean Pierre ; Vidal, Sébastien. / Synthesis of a C-glucosylated cyclopropylamide and evaluation as a glycogen phosphorylase inhibitor. In: Bioorganic and Medicinal Chemistry Letters. 2008 ; Vol. 18, No. 17. pp. 4774-4778.
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