AN ENZYMIC SYNTHESIS OF PURINE D-ARABINONUCLEOSIDES

Article abstract of DOI:10.1016/S0008-6215(00)80531-5

A method is described for the synthesis of purine D-arabinonucleosides that uses purine bases and 2,2'-anhydro-(1-β-D-arabinofuranosylcytosine), AraC-an, as the starting materials.AraC-an was chosen as the precursor to the D-arabinosyl donor, because it is more readily available than any of the products that may be sequentially derived from it, namely, 1-β-D-arabinofuranosylcytosine ( AraC ), 1-β-D-arabinofuranosyluracil ( AraU ), and α-D-arabinofuranosyl-1-phosphate ( Araf 1-P ), a D-arabinofuranosyl donor.Four reactions were involved in the ovarall procass; ( a ) AraC-an was nonenzymically hydrolyzed at alkaline pH to AraC which was then ( b ) deaminated by deaminase to AraU, a nucleoside, ( c ) phosphorylyzed by uridine phosphorylase to Araf 1-P, and ( d ) this ester caused to react with a purine base to afford a purine D-arabinonucleoside, the reaction being catalyzed by purine nucleoside phosphorylase.All four rections occured in situ, the first and second being performed sequentially, whereas the third and fourth were combined in a single step.The three enzyme catalysts were purified from Escherichia coli.The efficiency of the method is exemplified by the synthesis of the D-arabinonucleosides of 2,6-diaminopurine and adenine; the overall yields, based on AraC-an, were 60 and 80 percent respectively.