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Mono, di and tri-mannopyranosyl phosphates as mannose-1-phosphate prodrugs for potential CDG-Ia therapy. 2007
Renaud Hardré, and
Amira Khaled, and
Alexandra Willemetz, and
Thierry Dupré, and
Stuart Moore, and
Christine Gravier-Pelletier, and
Yves Le Merrer
Université René Descartes, UMR 8601 CNRS, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, 45 rue des Saints-Pères, 75006 Paris, France.
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.
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