Cyclic bis(3'-5')diadenylic acid (c-di-AMP) (Chart I), recently identified as a second messenger monitoring DNA integrity during sporulation in the soil bacterium Bacillus subtilis, was synthesized on an 80 mu mol scale by a combination of the phosphoramidite and phosphotriester methods using a commercially available adenosine phosphoramidite as starting material. An artificial analog 2'-bis(tert-butyldimethylsilyl)-c-di-AMP was also obtained by our procedure.