Mini-Review of the Phosphate Center Activation Strategy in Nucleoside Triphosphate Preparation

Background: Nucleoside triphosphates (NTPs) synthesis has recently been an area of searching for new methods and possible applications in biochemistry and medicine. However, we still lack a universal tool to synthesize NTPs easily and efficiently. For years, the most popular method has been the “one-pot, three step” conception by Ludwig with its subsequent improvements which used Yoshikawa's et al. monophosphorylation method. Further investigation of these reactions has proven many disadvantages: low yields, many byproducts and problems with purification. But they were a starting point for a whole branch of NTPs synthetic methods. Method: Analysis of this evolution process demonstrates some correctness: using a pyrophosphate as a nucleophile and mechanism involving a cyclic intermediates at some stage. What is changing is the idea of phosphorus center activation and the resulting improvements and limitations. Conclusion: In this paper we would like to discuss some new achievements in NTPs synthesis considering their role in changing the strategy of phosphorus center activation depending on the needs