Abstract A practical method for synthesis and isolation of previously elusive
deprotected P-N linked foscarnet-amino acid conjugates was developed. The conjugates are good candidates for evaluation as foscarnet prodrugs as they release the active drug quantitatively under
physiological conditions leaving only benign amino acids as by-products. A number of alkyl ester-protected thiophosphonoformate-peptide conjugates were synthesized via coupling between dimethyl-TPFACl and C-alkyl protected amino acids. An easily scalable, safe and cleaner method for synthesis of dimethyl-TPFACl was developed. The conjugates were treated with a series of dealkylating agents, such as t-BuNH2, NaOH, NaI, LiBr…
