Process for preparation of cyclic prodrugs of pmea and pmpa

Abstract From the Canadian patent

The method of preparing compounds of Formula I is described: Formula Iwherein:M and V are cis to one another and MPO3H2 is a phosphonic acid selected from the group consisting of 9-(2-phosphonylmethoxyethyl)adenine and , (R)-9-(2-phosphonylmethoxypropyl)adenine; wherein V is phenyl optionally , substituted with 1-2 substituents selected from a group consisting of fluoro chloro, and bromo; comprising:coupling a chiral 1-phenylpropane-1,3-diol wherein the phenyl may be optionally substituted with MPOCl2 or an N-6 , substituted analogue thereof.Additionally methods and salt forms are , described that enable isolation and purification of the desired isomer.