title: Spiro sugar-isoxazolidine scaffold as useful polyfunctional building block for peptidomimetics design.
abstract: Spiro sugar-isoxazolidines obtained by 1,3-dipolar cycloaddition of activated exo-glycals and nitrones were efficiently functionalized at two sites, i.e. C-4 and C-7, with arginine, arginine mimetics and guanidylated appendages. Two bicyclic sugar derivatives differing by the configuration at C-7 were chosen as model compounds. The small library of peptidomimetics was evaluated toward inhibition of VEGF-A165/neuropilin-1 binding. Unexpected cleavage of C3-C4 bond of isoxazolidine moiety was observed during hydrogenolysis and opened thus a new way toward hemiketal structures which could also find interesting applications as less constrained scaffold.
authors: Université de Lorraine, UMR 7565 SRSMC, F-54506, Nancy, France; CNRS, UMR 7565 SRSMC, F-54506, Nancy, France.
authors: Mylène
authors: M
authors: Richard
authors: Université de Lorraine, UMR 7565 SRSMC, F-54506, Nancy, France; CNRS, UMR 7565 SRSMC, F-54506, Nancy, France.
authors: Yves
authors: Y
authors: Chapleur
authors: Université de Lorraine, UMR 7565 SRSMC, F-54506, Nancy, France; CNRS, UMR 7565 SRSMC, F-54506, Nancy, France. Electronic address: nadia.pellegrini@univ-lorraine.fr.
authors: Nadia
authors: N
authors: Pellegrini-Moïse
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D061565:Cycloaddition Reaction; D015195:Drug Design; D007555:Isoxazoles / Q000737:chemistry*; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry*; D013141:Spiro Compounds / Q000737:chemistry*
chemical_list: D002241:Carbohydrates; D007555:Isoxazoles; D057786:Peptidomimetics; D013141:Spiro Compounds
keywords: Isoxazolidine; Nitrone cycloaddition; Peptidomimetic; Sugar scaffold; exo-Glycal