Preparation and characterization of potential prodrugs of dyphylline

Four diesters and four monoesters of dyphylline were synthesized as prodrugs proposed to prolong the duration of action of dyphylline. They were characterized by IR, 1H NMR, HPLC, and MS. Appropriate solvent-programming conditions for the HPLC separation of dyphylline and the newly synthesized mono- and diesters were developed. It was confirmed by low-temperature 1H NMR at approximately -40 degrees C that all four monoesters were located on the primary hydroxy position. Attempts to produce the secondary monoesters yielded the primary monoesters during purification. Monoesters were shown by HPLC and MS to migrate between the primary and secondary hydroxy groups in aqueous solution.