Cyclotriphosphate: A Brief History, Recent Developments, and Perspectives in Synthesis

There has been a recent upsurge in the study and application of approaches utilizing cyclotriphosphate 1 (cyclo-TP, also known as trimetaphosphate, TMP) and/or proceeding through its analogues in synthetic chemistry to access modified oligo- and polyphosphates. This is especially useful in the area of chemical nucleotide synthesis, but by no means restricted to it. Enabled by new high yielding and easy-to-implement methodologies, these approaches promise to open up an area of research that has previously been underappreciated. Additionally, refinements of concepts of prebiotic phosphorylation chemistry have been disclosed that ultimately rely on cyclo-TP 1 as a precursor, placing it as a potentially central compound in the emergence of life. Given the importance of such concepts for our understanding of prebiotic chemistry in combination with the need to readily access modified polyphosphates for structural and biological studies, this paper will discuss selected recent developments in the field of cyclo-TP chemistry, briefly touch on ultraphosphate chemistry, and highlight areas in which further developments can be expected.