From 2-FddA to 3-FddG: A journey in the fluorination of purine nucleosides


Kunisuke Izawa, Ajinomoto Co., Inc, Japan
The fluorination of organic compounds often leads to a dramatic change in their biological activity. As a result, many fluorine-containing pharmaceuticals have been approved by the FDA over the past few decades. Recently, fluoro-nucleosides such as 2′β-FddA and 3′α-FddG have attracted much attention due to their high potency against HIV reverse transcriptase. We have successfully developed efficient and economical processes for both compounds from readily available inosine and guanosine respectively. In each case, fluorination proved to be the crucial synthetic step. By selecting the appropriate substrate and reaction conditions, fluorination was achieved with safe and inexpensive reagents.