GDP-Activated Donors

D-Mannose and L-fucose are related biogenetically and are transferred from their corresponding guanosine diphosphate-activated donors [57] by the corresponding transferases. GDP-Man constitutes an a-phosphate whereas in GDP-Fuc the diphosphate bridge is P-linked to the fucose unit. 

Always only one residue is altered, the remaining residues are either OH for Ra, Rb, Rc or CH3 for Rj. 

Spacer = fluorescent label added to spacer H2N CH2)2S(CH2)20CH2-, C5H11-, C7H15-. 

The critical intermediate in the outlined synthesis is the p-fucosyl phosphate, which can hardly be separated cleanly from the concomitant a isomer [65, 70], The ensuing coupling to the morpholidate-activated GMP proceeds sluggishly and is always accompanied by epimerization and hydrolysis. TTiis makes the synthesis a low-yielding process and impedes the isolation of the pure GDP-fucose from this reaction mixture. 

The first hurdle which must be overcome in the chemical synthesis of sugar nucleotides is the preparation of anomerically pure sugar phosphates. In sialic acid there is no neighboring group which can control the stereoselective phosphorylation of the C-2 center to form the desired P-phosphates selectively. Optimization of protecting groups and phosphorylation protocols led to modest improvements only of the a/p ratios. This problem is not yet solved satisfactorily. 

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