Attempted synthesis of Regadenoson and Cangrelor by Aglycon Swapping Editing Reaction (ASER)

Abstract

Conventional synthesis of adenosine-based drugs such as Regadenoson and Cangrelor involve multistep procedures that utilize toxic reagents, metal catalysts, and environmentally unsafe solvents. A greener and unified synthetic approach using adenosine as a renewable and naturally derived precursor is warranted. Our ASER methodology exploits the inherent functionality of adenosine, enabling selective modifications on both the purine ring and ribose framework under mild and sustainable conditions. Key transformations include regioselective substitution and coupling reactions mediated by triphenylphosphine/DIAD and sodium methoxide in methanol, eliminating the need for heavy metals and minimizing waste generation. This approach significantlyimproves atom economy, reduces purification steps, and operates efficiently at ambient conditions. The route not only allows the synthesis of Regadenoson and Cangrelor through a common intermediate but also offers a versatile platform for developing a broader range of adenosine-derived analogues