Synthesis of pyrazofurin and its analogues

Abstract

Pyrazofurin and its analogues have been synthesized from ribosyl β-keto acid derivatives, which can be readily prepared by Wittig reaction of the protected D-ribose with phosphoranes.

Reaction of 2,3-O-isopropylidene-5-O-trityl-α- and -β-D-ribose (6) with 3-ethoxycarbonyl-2-oxo-propylidenetriphenylphosphorane (8a) gave ethyl 4-(2′,3′-O-isopropylidene-5′-O-trityl-α- and -β-D-ribofuranosyl)-3-oxobutanoate (10a). The β-keto ester (10a) was treated with tosyl azide in the presence of triethylamine to afford ethyl 2-diazo-4-(2′,3′-O-isopropylidene-5′-O-trityl-α- and -β-D-ribofuranosyl)-3-oxobutanoate (11a) which, on treatment with sodium hydride, cyclized to ethyl 4-hydroxy-3-(2′,3′-O-isopropylidene-5′-O-trityl-β-D-ribofuranosyl)pyrazole-5-carboxylate (16β) and the α-anomer (16α). Ammonolysis of (16β) and (16α) afforded the corresponding amides (19β) and (19α) which, after moval of the protecting groups, gave pyrazofurin (1) and pyrazofurin B (2) respectively. Pyrazofurin nalogues (3), (4), and (5) were also synthesized by analogous procedures.