An alternative synthesis of HPMPC and HPMPA diphosphoryl derivatives

In (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC) and (S)-9-[ 3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA) with 3-hydroxy functio ns protected with 4,4'-dimethoxytrityl (DMTr) groups, phosphonate groups we re transformed to the morpholides and treated with bis(tributylammonium) di phosphate, Selective cleavage of the DMTr group in the presence of the labi le diphosphate residue was achieved in water at pH 2.5. Purification by cha rcoal adsorption followed by anion exchange chromatography afforded phospho nate-diphosphate compounds (HPMPCpp, HPMPApp).