Regiospecific and Highly Stereoselective Electrophilic Addition to Furanoid Glycals: Synthesis of Phosphonate Nucleotide Analogues with Potent Activity against HIV

Article abstract of DOI:10.1021/jo00008a013

Regiospecific and highly stereoselective electrophilic addition to furanoid glycals has been used as a key step in the synthesis of phosphonate isosteres of nucleoside monophosphates.Using this methodology, phosphonate analogues of 1 (ddA), 4 (d4T), and 5 (d4A) monophosphates have been prepared.Present studies have also led to the development of a scheme for the synthesis of the phosphonate isostere of adenosine monophosphate.Despite the acetal structure, phosphonate derivatives 27 and 28 were substantially more acid stable than the corresponding nucleosides 1 and 5 with respect to glycosidic bond cleavage.The phosphonates 22 and 27 exhibited a potent antiretroviral activity comparable to that of 4 (d4T).