Keto and Exomethylene Pyranonucleosides as Antitumor Agents

E.      Tsoukala; S.      Manta; C.      Kiritsis; D.      Komiotis

Abstract

Nucleosides and their analogues take an important place in medicinal chemistry as the structural basis for the development of therapeutic agents. Recently, there has been a renewed interest in the synthesis of keto and exomethylene pyranonucleosides, due to their high cytotoxicity in vitro and powerful inhibitory action in vivo. Their mode of action probably involves their ability to act as acceptors in a Michael-addition mechanism, while it was revealed that 5- fluorouracil nucleosides represent novel prodrugs of 5-fluorouracil targeting thymidylate synthase. The present mini review summarizes the molecular design, chemical synthesis and biological activity of keto- and exomethylene pyranonucleoside analogues.

Keywords: pyranonucleosides, ketonucleosides, exomethylene nucleosides, oxidation, Wittig reaction, cytotoxicity, antitumor activity, tributyltin hydride, N-bromosuccinimide, adenocarcinoma, triphenylphosphonium bromide, p-toluenesulfonic acid, triphenylphosphine, 5-fluorouracil, tert-butyldimethylsilyl chloride