An H-Phosphonate-Mediated Synthesis of Nucleotide-Pyranose Glycoconjugates
Thibault Guillaume1, Ningwu Huang2, Mark Smith2
1School of Chemical and Physical Sciences, Keele University, Keele, Staffordshire ST5 5BG, U.K.
Abstract:
We explore a synthesis of nucleotide-pyranose conjugates, successfully developing an H-phosphonate-mediated coupling of pyranoses with nucleosides that favors making the reactive phosphorus(III) species within the pyranose (C6-OH or C1-OH) and affords, after oxidation to the free phosphate, glycoconjugates in good overall yields (65-84%). Following deprotection and final purification, the materials are evaluated in U87-MG and PANC-1 cells, with activities comparable to the parent drugs, indicating such conjugates worthy of deeper validation as prodrugs.
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