6-chloroxanthosine, a useful intermediate for the efficient syntheses of [6-N-15]-isoguanosine, isoinosine and other purine nucleoside analogues

6-Chloroxanthosine 1, when activated towards nucleophilic displacement at the 6-C position by conversion into the corresponding 3-N-(2,4-dinitrophenyl) derivative 4, reacted with aq. (NH3)-N-15 to afford [6-N-15]-isoguanosine 3b in 81% overall yield. Catalytic hydrogenation (Pd/C) of 1 led in 60% yield to isoinosine 8; alternatively, this could be obtained in 88% overall yield through alkaline hydrolysis of triphenylphosphonium salt 6, synthesized from 1 by reaction with PPh(3). The reactivity of 1 was further explored by treating it with primary and secondary amines: the 6-N propylamino and the 6-N piperidinyl derivatives (5a and 5b, respectively) could thus both be prepared in more than 90% yield.