SYNTHESIS OF ADENOSINE CYCLIC 3',5'-PHOSPHOROFLUORIDATE (CAMP-F)

Work aimed at the chiral synthesis of both diastereomers of adenosine cyclic 3',5'-phosphorofluoridate, cAMP-F 7, is described. Attempted debenzoylation of the intermediate N-6,N-6,O-2'-tribenzoyladenosine cyclic 3',5'-phosphorofluoridate 4 by ammonolysis resulted in cleavage of the P-F bond. Reaction of [Sp]-S-methyl adenosine 3',5'-cyclophosphorothioate 6 with AgF gives a mixture of the two diastereoisomers of the cyclic phosphorofluoridate 7 along with adenosine 2',3'-cyclic phosphate 8. The conversion of 7 into 8 can be completed under remarkably mild conditions. Possible mechanisms for this unusual transformation are discussed.