A Simple Solution to the Age Old Problem of Regioselective Functionalization of Guanine:  First Practical Synthesis of Acyclic N⁹- and/or N⁷-Guanine Nucleosides Starting from N²,N⁹-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 N(7) and N(9) isomers, respectively, appear to follow different mechanisms. The practical utility of the noncatalyzed reaction, which gives almost quantitative yields of N(9) derivatives, is demonstrated by synthesizing acylovir/gancyclovir in high yields.