An unambiguous synthesis of adenylosuccinic acid and its constituent nucleoside

Abstract

6-(4-Chlorophenylthio)-9-(2,3-O-cyclopentylidene-β-D-ribofuranosyl)-9H-purine(7) is prepared from 6-chloro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-9H-purine (5) in three steps and is then converted, by treatment with 3-chloroperbenzoic acid, into the corresponding sulphoxide (9) and crystalline sulphone (8) in ca. 88 and 65% isolated yield, respectively. When the sulphoxide (9) is heated with dibenzyl L-aspartate in N,N-dimethylacetamide solution at 70–75 °C for 28 hr, compound (11) is obtained in ca. 70% isolated yield. Removal of the protecting groups from compound (11) gives N-[9-(β-D-ribofuranosyl)-9H-purin-6-yl]-L-aspartic acid (3) as a crystalline solid in ca. 68% yield; phosphorylation of compound (11) with dibenzyl phosphorochloridate and removal of the protecting groups gives adenylosuccinic acid (1), isolated as its ammonium salt, in ca. 66% yield. When the sulphone (8) is converted via compound (11) into the diacids (3) and (1), the products obtained appear to be contaminated with the D-acids (12) and (14), respectively, which are diastereoisomers of compounds (3) and (1).