Highly efficient chemical phosphorylation of 6-(4-phenylpiperazine-1-yl)-9-(β-D-ribofuranosyl)-9H-purine

Abstract

Antimetabolites, which are metabolic antagonists used in the treatment of cancer and viral diseases by replacing metabolites, inhibit the action of metabolic enzymes and disrupt the pathways of synthesis of structural units necessary for the formation of nucleic acids. Purine antagonists, that are subunits of antimetabolites, reduce the production of purine bases, and hence, cause the nucleotide production to stop and bring about the death of cancer cells. Fludarabine (2-fluoro-ara-AMP), which is used in chemotherapy, is an antimetabolite of the purine class containing mono phosphate in its structure. In this study, a protocol was presented to effectively and efficiently synthesis of 6-(4-phenylpiperazine-1-yl)-9-(β-D-ribofuranosyl)-9H-purine-5’- O-phosphate compound in six steps and 25% overall yield starting with commercially available 6-chloropurine.

Keywords:

• Nucleoside-5’-O-phosphate analog
• microwave-assisted synthesis
• phosphorylation

Additional information

Funding

This work was supported by the Scientific and Technological Research Council of Turkey-TUBITAK (SBAG-112S182).