Three 2'-modified cyclic bis(3'-5')diadenylic acids (c-di-AMPs) were synthesized from commercially available adenosine phosphoramidites and the effects of c-di-AMP derivatives on the cell division of Chlamydomonas reinhardtii, a kind of freshwater green algae, were investigated. This structure-activity relationship study suggests that the di(2'-O-methyl)-c-di-AMP showed the highest activity and that 2'-substituents influenced the cell division of C. reinhardtii.