Synthesis of Some Novel ۸-Piperazinyl Caffeine Acetic Acidβ-hydroxyester Derivatives as Potential Anticancer Agents

In this paper, the synthesis and characterization of novel ۸-piperazinyl caffeine acetic acid β- hydroxyester derivatives as potential antimetabolites and anticancer agents have been described. These compounds are new caffeine hybrid molecules that are structurally composed of three compartments comprising caffeinyl, piperazinyl andβ-hydroxyester residues. The synthesis was carried out through five steps initiated by the bromination of caffeine via NBS to attain the ۸-bromocaffeine (۸-BC) followed by the SNAr-type reaction with the piperazine which afforded the ۸-piperazinyl caffeine (۸- PC). The N-alkylation of ۸-PC with α-bromo acetic acid ethyl ester acquired the ester ۹. Ester ۹ was then hydrolyzed followed by an acidic work up to give acid ۱۰. Acid ۱۰ was used to ring opening of diverse epoxides to attain the title compounds ۱۱a-۱۱j in good yields. Target compounds were characterized using vary physical and spectral techniques.

Keywords:

caffeine , ۸-BC , ۸-PC , piperazine , -hydroxyester , antimetabolites