Abstract An improved procedure for the chemical synthesis of coenzyme A by anhydride-anion exchange is described. A mixture of the 2′,5′- and 3′,5′-diphosphastes of adenosine is treated with diphenylphosphorochloridate to give P 1 -adenosine (2′3′-cyclic phosphate)-5′- P 2 -diphenylpyrophosphate quantitatively. This is then treated with pantethine 4′,4′- bis -phosphate in pyridine to give a 2′,3′-cyclic phosphate form of coenzyme A with displacement of diphenylphosphate from the intermediate mixed anhydride. Specific enzymic opening of the cyclic phosphate gives coenzyme A in high yield. A synthesis of guanosine 2′(3′),5′-diphosphate is also described.