Department of Chemistry, Massachusetts Institute of Technology, Cambridge Massachusetts 02139, United States.
Institute of Organic Chemistry, University of Freiburg & Cluster of Excellence livMatS, FIT - Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg, Georges-Köhler-Allee 105, D-79110 Freiburg, Germany.
J Am Chem Soc. 2022 May 4;144(17):7517-7530. doi: 10.1021/jacs.1c07990. Epub 2022 Apr 26.
Oligophosphates play essential roles in biochemistry, and considerable research has been directed toward the synthesis of both naturally occurring oligophosphates and their synthetic analogues. Greater attention has been given to mono-, di-, and triphosphates, as these are present in higher concentrations biologically and easier to synthesize. However, extended oligophosphates have potent biochemical roles, ranging from blood coagulation to HIV drug resistance. Sporadic reports have slowly built a niche body of literature related to the synthesis and study of extended oligophosphates, but newfound interests and developments have the potential to rapidly expand this field. Here we report on current methods to synthesize oligophosphates longer than triphosphates and comment on the most important future directions for this area of research. The state of the art has provided fairly robust methods for synthesizing nucleoside 5'-tetra- and pentaphosphates as well as dinucleoside 5',5'-oligophosphates. Future research should endeavor to push such syntheses to longer oligophosphates while developing synthetic methodologies for rarer morphologies such as 3'-nucleoside oligophosphates, polyphosphates, and phosphonate/thiophosphate analogues of these species.
寡磷酸盐在生物化学中起着重要作用，人们已经对天然寡磷酸盐及其合成类似物的合成进行了大量研究。人们更加关注单、二和三磷酸盐，因为这些在生物体内的浓度更高，并且更容易合成。然而，长链寡磷酸盐具有强大的生化作用，从血液凝固到 HIV 耐药性都有涉及。零星的报道逐渐形成了与长链寡磷酸盐的合成和研究相关的专门文献，但新的兴趣和发展有可能使这个领域迅速扩大。在这里，我们报告了目前合成长于三磷酸盐的寡磷酸盐的方法，并对该研究领域的最重要未来方向进行了评论。目前的技术已经为合成核苷 5'-四磷酸和五磷酸以及二核苷酸 5'，5'-寡磷酸盐提供了相当可靠的方法。未来的研究应该努力将这些合成方法推进到更长的寡磷酸盐，同时开发出更罕见形态的合成方法，如 3'-核苷寡磷酸盐、多磷酸盐以及这些物质的磷酸酯/硫代磷酸酯类似物。
