A General Strategy to Synthesize ADP-7-Azido-heptose and ADP-Azido-mannoses and Their Heptosyltransferase Binding Properties
Tianlei Li, Abdellatif Tikad, Huixiao Fu, Jozafina Milicaj, Colleen D. Castro, Marine Lacritick, Weidong Pan, Erika A. Taylor, Stéphane P. Vincent
Abstract
The multistep synthesis of a novel ADP-7-azido-7-deoxy-l-glycero-β-d-manno-heptopyranoside 2a and several analogues as heptosyltransferase ligands is described. The synthesis of the key intermediate heptoside-1-β-phosphate 3a involved a β-stereoselective phosphorylation of lactol 4 employing diallyl chlorophosphate as a phosphorylating reagent. Five deprotected nucleotide sugars were generated by this synthetic sequence and evaluated as heptosyltransferase substrates (KM, kcat).
Topics & Concepts
ChemistryStereoselectivityNucleotideStereochemistryPhosphorylationReagentHeptoseCombinatorial chemistrySequence (biology)LactolBiochemistryLactoneCatalysisOrganic chemistryMutantGeneCarbohydrate Chemistry and SynthesisBiochemical and Molecular ResearchDiet, Metabolism, and Disease