AZTppppA is the product of AZT excision associated with HIV RT drug resistance. Its hydrolysis-resistant analogs, AZTp_Sp_CX2pp_SA (X = H or F), can be used to study the inhibition of AZT excision and may be inhibitors of the excision reaction. An efficient method was developed to synthesize AZTp_Sp_CX2pp_SA (X = H or F) with total yields up to 80%. The four diastereomers of each product were separated and purified, and their configurations were identified by enzymatic degradation.