Synthesis of Novel Thiopurine Pyranonucleosides: Evaluation of Their Bioactivity

Abstract

We report the synthesis of novel thiopurine pyranonucleosides. Direct coupling of silylated 6-mercaptopurine and 6-thioguanine with the appropriate pyranoses 1a–e via Vorbrüggen nucleosidation, gave the N-9 linked mercaptopurine 2a–e and thioguanine 4a–e nucleosides, while their N-7 substituted congeners 10a–e and 7a–e, were obtained through condensation of the same acetates with 6-chloro and 2-amino-6-chloropurines, followed by subsequent thionation. Nucleosides 3a–e, 5a–e, 8a–e, and 11a–e were evaluated for their cytostatic activity in three different tumor cell proliferative assays.

Keywords:

• 6-Mercaptopurine
• 6-thioguanine
• 6-chloropurine
• 2-amino-6-chloropurine
• pyranonucleosides
• cytotoxic activity