REGIOSPECIFIC AND HIGHLY STEREOSELECTIVE ELECTROPHILIC ADDITION TO FURANOID GLYCALS - SYNTHESIS OF PHOSPHONATE NUCLEOTIDE ANALOGS WITH POTENT ACTIVITY AGAINST HIV

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).