A new chemical synthesis of 2-amino-(N-d-ribofuranosyl)acetamide 5′-phosphate

2-amino-(N-d-ribosyl)acetamide 5′-phosphate (GAR, 10) has been prepared in a readily scaled-up synthesis from 2,3-O-isopropylidene-d-ribofuranosylamine p-toluenesulfonate (3) by condensation with the mixed anhydride of N-(benzyloxy-carbonyl)glycine, followed by phosphorylation with 2-cyanoethyl phosphate and removal of the protecting groups. By varying the conditions, the α-4 and the β-5 anomers could be obtained and separated from each other. Anomerization occurs upon removing the O-isopropylidene group from either 7 or 8, so that the final compound (10) is an equimolar mixture of both anomers, of which only one is active toward GAR-transformylase.