Beyond Triphosphates: Reagents and Methods for Chemical Oligophosphorylation

Oligophosphates play essential roles in biochemistry, and considerable research has been directed toward thesynthesis 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, extendedoligophosphates have potent biochemical roles, ranging from blood coagulation to HIV drug resistance. Sporadic reports have slowlybuilt a niche body of literature related to the synthesis and study of extended oligophosphates, but newfound interests anddevelopments have the potential to rapidly expand thisfield. Here we report on current methods to synthesize oligophosphateslonger than triphosphates and comment on the most important future directions for this area of research. The state of the art hasprovided 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 syntheticmethodologies for rarer morphologies such as 3 '-nucleoside oligophosphates, polyphosphates, and phosphonate/thiophosphateanalogues of these species

Automated summary

Oligophosphates play important roles in biochemistry, and research has focused on the synthesis of both natural and synthetic oligophosphates. While mono-, di-, and triphosphates have received more attention due to their biological relevance and ease of synthesis, extended oligophosphates also have significant biochemical functions. Current methods for synthesizing longer oligophosphates have been fairly successful, and future research should aim to push the synthesis further while developing methods for rare morphologies.