Synthèse de glycosides de conformation contrainte en vue de l'inhibition d'hexosaminidases

Translated title of the thesis: Synthesis of conformationally constrained glycosides as hexosaminidases inhibitors
  • Olivier Massinon

Student thesis: Doc typesDoctor of Sciences


The aim of the project is the synthesis of conformationally 1,4B boat locked glycosides, as inhibitors and mechanistic probes of a family of glycosidases called hexosaminidases.
Hexosaminidases play a significant role in numerous biological processes and are widespread among living organisms. The inhibition of these enzymes has been extensively studied during the last years in order not only to improve our knowledge about their structure, mechanism and biological roles, but also to develop therapeutic agents in the treatment of serious diseases.
These enzymes catalyze the hydrolysis of N-acetylhexosamine residues, in particular N-acetyl-glucosamine (GlcNAc), from polysaccharides and other glycoconjugates. They mainly proceed via retention of the anomeric configuration. Interestingly, they seem to bind and stabilize their substrates in a high energy conformation, located between a 1,4B boat and a 1S3 skew boat. Thus, conformationally 1,4B boat locked compounds may constitute very efficient inhibitors and could allow us to investigate the involvement of this conformation in the mechanism.
First, a set of bicycles [2.2.1] was synthesised based on a 1,4B Boat locked GlcNAc. Then, these molecules were assayed against hexosaminidases from different families to measure their inhibition activities and potential selectivities.
Date of Award23 Nov 2015
Original languageFrench
Awarding Institution
  • University of Namur
SupervisorStephane VINCENT (Supervisor), Johan Wouters (President), STEVE LANNERS (Jury), Yves Bleriot (Jury) & Tony Lefebvre (Jury)


  • Organic chemistry
  • Glycochemistry

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