Palladium-Catalyzed Cyanation of Nucleobases: Total Synthesis of Toyocamycin, Sangivamycin, and a Mycalisine A Precursor

Abstract

Installation of cyano (CN-) functionality onto nucleosides has always been a challenging task for chemists and catalytic protocols developed for simple aryl substrates in most cases have failed to replicate their success when applied to nucleobase or sugar moiety of nucleosides. Given the importance of the cyano and amide functionalities in nucleoside chemistry, we herein disclose an efficient Pd-catalyzed cyanation protocol specifically applied to iodo-nucleobases. Furthermore, the developed methodology of cyanation has been explored for synthesis of naturally occurring and bio-active nucleosides such as toyocamycin, sangivamycin and Mycalisine A precursor has been demonstrated.