P¹,P²-Diimidazolyl derivatives of pyrophosphate and bis-phosphonates – synthesis, properties, and use in preparation of dinucleoside tetraphosphates and analogs

Abstract

P1, P2-Diimidazolyl derivatives of pyrophosphate and halomethylene-bis-phosphonates have been synthesized and characterized, and the mechanism of their formation was studied. These reagents enable synthesis of dinucleoside tetraphosphates and tetraphosphonates conveniently and in high yields.

Cap analogs modified with 1,2-dithiodiphosphate moiety protect mRNA from decapping and enhance its translational potential

“…The bond is formed in a reaction of P -nucleophilic and P -electrophilic subunits (usually nucleotides 5′-substituted by an activating group (28–30), which is often mediated by divalent cations in an aprotic polar solvent (31,32). We previously implemented this general method to synthesize cap analogs using P -imidazolides as P -electrophiles, phosphate-modified or unmodified nucleotides as nucleophiles and ZnCl 2 or MgCl 2 as catalysts (33).…”

New highly active antiplatelet agents with dual specificity for platelet P2Y1 and P2Y12 adenosine diphosphate receptors

“…This is due, in part, to the lack of a chemical method allowing rapid synthesis in good yield of new Ap 4 A analogs. We have recently reported synthesis and properties of new reagents, diimidazolyl derivatives of diphosphoric and (methylene)bisphosphonic acids, which allow rapid synthesis of dinucleoside tetraphosphates in high yields [39]. We explored this method to prepare a number of new Ap 4 A analogs with modifications in the adenosine base and the tetraphosphate moiety, and now report on their synthesis, their properties as platelet aggregation inhibitors and their activities toward platelet purinergic (P2) receptors.…”

Phosphate-modified analogues of m 7 GTP and m 7 Gppppm 7 G—Synthesis and biochemical properties

“…In the reverse approach an inorganic phosphate or pyrophosphate is activated with imidazole and then coupled with a non-activated nucleotide. [29][30][31] One example of such an approach has been applied to the synthesis of diuridine and diadenosine tetraphosphates and their a,d-dithio analogues, by coupling 2 equiv of an appropriate nucleotide mono(thio)phosphate with 1 equiv of pyrophosphate P 1 ,P 2 -di(1-imidazolyl) derivative. 29 To obtain nucleotides additionally containing a methylene bridge in the b,c-position, activated phosphonate has also been developed.…”

“…[29][30][31] One example of such an approach has been applied to the synthesis of diuridine and diadenosine tetraphosphates and their a,d-dithio analogues, by coupling 2 equiv of an appropriate nucleotide mono(thio)phosphate with 1 equiv of pyrophosphate P 1 ,P 2 -di(1-imidazolyl) derivative. 29 To obtain nucleotides additionally containing a methylene bridge in the b,c-position, activated phosphonate has also been developed. Here, we used a similar strategy to obtain bis (7-methylguanosine) tetraphosphates, and their a,d-dithio and a,d-diborano analogues optionally containing a b,c-methylene group.…”