How To Form a Phosphate Anhydride Linkage in Nucleotide Derivatives

Abstract

The fundamental roles of nucleoside triphosphates and nucleotide cofactors such as NAD(+) in biochemistry are well known. In recent decades, continuing research has revealed the key role of 5'-capped RNA and 5',5'-dinucleoside polyphosphates in the regulation of vitally important physiological processes. Last but not least, the commercial potential of nucleoside triphosphate synthesis can hardly be overestimated. Nevertheless, despite decades of investigation and the obvious topicality of the research on the chemical synthesis of the nucleotide compounds containing phosphate anhydride linkages, none of the existing procedures can be considered an up-to-date "gold standard". However, there are a number of fruitful synthetic approaches to forming phosphate anhydride linkages in satisfactory yield. These are summarized in this concise review, organized by the type of active phosphorous intermediate and reagents used.

Recent Trends in Nucleotide Synthesis

“…Similarly to 1 H and 13 C, 31 P has a spin quantum number of 1 / 2 , but in contrast, 31 P is the only natural isotope of the phosphorus element. Although the nucleus has a rather low sensitivity (ca.…”

Rapid Synthesis of Nucleoside Triphosphates and Analogues

“…In most cases, the triphosphorylation is the most challenging step of NTP synthesis. Several approaches for synthesizing NTPs have previously been reported and are summarized in various reviews and book chapters (Burgess & Cook, 2000;Duro, Mustafa, Kashemirov, & McKenna, 2019;Hollenstein, 2012;Kore, & Srinivasan, 2013;Monir-Vaghefi, 2005;Roy et al, 2016;Sherstyuk & Abramova, 2015;Weinschenk & Meier, 2013). Despite their enormous range of biological functions, a universal synthesis procedure for all NTPs remains elusive (Liao et al, 2019).…”

Evaluation of Natural and Synthetic Phosphate Donors for the Improved Enzymatic Synthesis of Phosphate Monoesters

“…Synthesis of valuable phosphate (mono)esters, e. g. sugar phosphates,1, 2, 3 nucleotides,4,5 metabolites6,7 and prodrugs8, 9, 10 can be achieved by laborious chemical11, 12, 13, 14, 15, 16, 17, 18 or mild enzymatic routes 19, 20, 21. The latter usually employ kinases and ATP in conjunction with a second enzyme for the recycling of the phosphate donor.…”