engleski

Synthesis of 9-Sulfonylpurine Derivatives and Stability Enhancement with Small Structural Modifications

In continuation of our previous work on the synthesis and characterization of biologically active nucleobase derivatives, here we report on the synthesis of novel N-9-sulfonyl purine derivatives. Novel 6-chloro-N-9-sulfonyl purine derivatives I were prepared by the condensation reaction of 6-chloropurine with different sulfonyl chlorides in acetone and in the presence of aqueous KOH at 0 oC. The sulfonylation reaction occurred regioselectively at the purine N9 position lacking any concurrent N7 sulfonylation, as proved by the spectral data. It has been observed that all obtained compounds of type I tend to degrade in solution into starting 6-chloropurine and respective sulfonic acid. Degradation was determined by 1H NMR. It has been concluded that electronic effects of chloro-substituent at purine C-6 position may destabilize the N-S bond. Therefore, chlorine was substituted by electron-donating morfolino group giving II with dramatically increased stability in solution as determined by time-dependent 1H-NMR experiments. The latter reaction opens the way toward a new series of various 6-amino substituted N-9-sulfonylpurines II with increased stability which enables the assessment of their potential anticancer activity by systematic in vitro screening on tumor and normal human cells.

Purines ; Sulfonyl- Derivatives ; Sulfonylpurine Derivatives

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