The synthesis and in vitro anti-HIV activity of a novel series of pronucleotides are reported. These prodrugs were characterized by a phosphorodithiolate structure, incorporating two O-pivaloyl-2-oxyethyl substituents as biolabile phosphate protections. The compounds were obtained following an original one-pot three-step procedure, involving the formation of a phosphorodithioite intermediate which is in situ oxidized. In vitro, comparative anti-HIV evaluations demonstrate that such original prodrugs are able to allow the efficient intracellular release of the corresponding 5′-mononucleotide. The pronucleotide of 2′,3′-dideoxyadenosine (ddA) 3 exhibited a very potent antiretroviral effect with 50% effective concentration (EC₅₀) values in nanomolar concentration range in various cell lines. In primary monocytes/macrophages, this derivative was 500 times more potent in inhibiting HIV replication (EC₅₀ 0.23 pM) than ddA and the selectivity index of the prodrug is fifty times higher than the one of the parent nucleoside.

报道了一系列新型原核苷酸的合成和体外抗 HIV 活性。这些前药的特征在于二硫代磷酸酯结构，结合了两个O -pivaloyl-2-oxyethyl 取代基作为生物不稳定的磷酸盐保护。这些化合物是按照原始的一锅三步程序获得的，包括形成原位氧化的二硫代磷酸酯中间体。在体外，比较抗 HIV 评估表明，这种原始前药能够使相应的 5'-单核苷酸在细胞内有效释放。2',3'-双脱氧腺苷 (ddA) 3的前核苷酸在各种细胞系中表现出非常有效的抗逆转录病毒作用，在纳摩尔浓度范围内具有 50% 的有效浓度 (EC _{50 ) 值。在原代单核细胞/巨噬细胞中，该衍生物抑制 HIV 复制的效力 (EC 50} 0.23 pM) 是 ddA 的500 倍，前药的选择性指数是母体核苷的 50 倍。