Progress in the Functionalization of Purines and Purine Nucleosides by Minisci Reactions Over the Past 50 Years

Abstract

Over the past decade, significant progress has been witnessed in the functionalization of purines and purine nucleosides via Minisci reactions. This review primarily focuses on the latest advancements in applying Minisci reactions to purine bases, while also including some notable early examples, with an emphasis on the late-stage functionalization of purine nucleosides. The Minisci reaction, a radical-based method, enables direct C─H functionalization of purines, facilitating the incorporation of a wide range of functional groups under mild conditions. Key developments discussed in this review include the regioselective functionalizations at the C⁶, C⁸, and C² positions, which have greatly expanded the toolkit for nucleoside modification. Additionally, this review also explores mechanistic insights, as well as the role of catalysts and reaction conditions that enhance the selectivity and efficiency of these transformations. The progress in Minisci-type reactions offers valuable strategies for the synthesis of novel purine-based compounds with promising applications in drug discovery and development.