AN IMPROVED SYNTHESIS OF OLIGODEOXYRIBONUCLEOSIDE PHOSPHOROTHIOATES

已知反义硫代磷酸具有互补作用一段时间 对HIV-1rev基因的信使RNA抑制细胞病变 病毒对慢性感染的H9细胞的影响。可得性 因此，这些寡核苷酸类似物对生物医学至关重要 调查。 我们实验室最近报道了~3H-1，2-苯二硫酚-3-甲氧基苯并二硫醚的使用. 1，1-二氧化硫作为硫转移试剂在合成中的应用 硫代低聚脱氧核糖核苷。为了促进 硫转移试剂朱迪思·B·里根和 P.I.已经扩大并改进了试剂的制备。这 程序已在有机制剂和程序中发布 国际的。 硫代寡核苷酸对核酸酶具有天然的抵抗力 因此很难定性。一种便捷的方法 寡核苷硫代硫酸酯的表征将是 通过氧化脱硫法将它们转化为天然寡核苷酸。 我们的实验室投入了大量的精力来筛选各种 低聚核苷固相转化的氧化剂 将硫代三酯转化为相应的磷酸三酯。它 已发现0.05M的单过氧苯二甲酸溶液在 冰醋酸是一种理想的脱硫剂 硫代低聚物。然而，这种试剂导致了 胞嘧啶环链的修饰。寻找新的氧化剂的方法 放弃了硫代低聚物的脱硫。 此外，硫代低聚物转化为 另一类核酸酶抗性的磷酰胺寡核苷酸 寡核苷酸，已被研究，但尚未产生试剂 能够执行干净而快速的转换。

It is known for some time that antisense phosphorothioate complementary to the messenger RNA of the HIV-1 rev gene inhibited the cytopathic effect of the virus in chronically infected H9 cells. The availability of these oligonucleotide analogues is thus critical for biomedical investigations. Our laboratory has recently reported the use of 3H-1,2-benzodithiole-3- one 1,1-dioxide as a sulfur-transfer reagent in the synthesis of oligodeoxyribonucleoside phosphorothioates. To promote the accessibility of the sulfur-transfer reagent, Judith B. regan and the P.I. have scaled up and improved the preparation of the reagent. This procedure has been published in Organic Preparations and Procedures International. Oligonucleoside phosphorothioates are inherently resistant to nucleases and are therefore difficult to characterize. One approach to the facile characterization of oligonucleoside phosphorothioates would be to convert them to natural oligonucleotides via oxidative desulfurization. Our laboratory has invested considerable efforts in screening various oxidants for the solid-phase conversion of oligonucleoside phosphorothioate triesters to the corresponding phosphotriesters. It has been found that a 0.05 M solution of monoperoxyphthalic acid in glacial acetic acid was ideal for the desulfurization of phosphorothioate oligomers. However, this reagent caused the modification of the cytosine ring. The search for new oxidants for the desulfurization of phosphorothioate oligomer was abandoned. In addition, the conversion of phosphorothioate oligomers to phosphoramidate oligonucleotides, another class of nuclease-resistant oligonucleotides, has been investigated but has not led to a reagent capable of performing a clean and rapid conversion.