Cyclic diguanosine monophosphate (c-di-GMP) was first found to activate the synthesis of cellulose in Acetobacter xylium in 1987. It has recently been recognized that c-di-GMP is an important regulator of biofilm formation and other pathogenic processes in many types of bacteria. We have developed a new method to synthesize this molecule and its thioate analog (X=S), shown below.