A Simple Solution to the Age Old Problem of Regioselective Functionalization of Guanine: First Practical Synthesis of Acyclic <i>N</i>⁹- and/or <i>N</i>⁷-Guanine Nucleosides Starting from <i>N</i>²,<i>N</i>⁹-Diacetylguanine

Regioselective alkylation of guanine, a long-lasting challenge, has been overcome by understanding the role of acids as catalyst in the coupling reaction of DAG (10) with OBDDA (11). The acid-catalyzed and noncatalyzed reactions of 10 with OBDDA which mainly give N7 and N9 isomers, respectively, appear to follow different mechanisms. The practical utility of the noncatalyzed reaction, which gives almost quantitative yields of N9 derivatives, is demonstrated by synthesizing acylovir/gancyclovir in high yields