Mono, di and tri-mannopyranosyl phosphates as mannose-1-phosphate prodrugs for potential CDG-Ia therapy.
An efficient and convergent method for the synthesis of mannose-1-phosphate prodrugs is described as a potential therapy for congenital disorders of glycosylation-Ia (CDG-Ia). The key feature of the proposed approach is the silver assisted nucleophilic substitution of 2,3,4,6-tetra-O-protected-alpha-d-mannopyranosyl bromides with various silver phosphate salts to afford mono, di, and tri-mannopyranosyl phosphates. A preliminary biological evaluation of the synthesized phosphate prodrugs has been carried out.
Hardré
Renaud
R
Université René Descartes, UMR 8601 CNRS, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, 45 rue des Saints-Pères, 75006 Paris, France.
Khaled
Amira
A
Willemetz
Alexandra
A
Dupré
Thierry
T
Moore
Stuart
S
Gravier-Pelletier
Christine
C
Le Merrer
Yves
Y
D002240:Carbohydrate Sequence; D018981:Congenital Disorders of Glycosylation / Q000188:drug therapy*; D006801:Humans; D008360:Mannosephosphates / Q000737:chemistry*; D008969:Molecular Sequence Data; D010755:Organophosphates / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use
D008360:Mannosephosphates; D010755:Organophosphates; D011355:Prodrugs; C047217:mannose 1-phosphate