Modified Dinucleoside Tetraphosphonates, New Potential Inhibitors of Hiv Reverse Transcriptase

Abstract

New gamma-substituted analogues of dNTP were synthesized and their enzymatic stability and antiviral properties were evaluated.

Synthesis of α-brominated phosphonates and their application as phosphate bioisosteres

“…98 Carbocyclic dinucleoside polyphosphonates have shown activity against HIV reverse transcriptase-catalyzed DNA synthesis and hence demonstrate antiviral activity. 97,99 Polyphosphonate 58 displayed weaker anti-HIV activity than the equivalent CF 2 and P-O-P tetraphosphonate analogs. 99 It is important to note here that synthetic access to biologically interesting cyclic and acyclic a-uorophosphonate and a,a-diuorophosphonate nucleoside(-tide) analogs has been well studied and reviewed (e.g.…”

“…Commun., 2014, 5, 1619-1633 | 1629 highlight the syntheses that incorporate dibromo-polyphosphonate moieties into this class of molecules (Scheme 16). General access to these seemingly intricate brominated polyphosphonate analogs begins from bisphosphonate (54) and a carbodiimide (CDI)-activated phosphonate (55 97,98 or 57 99 ). Yields are generally moderate, and both the adenine and guanine analogs of carbocyclic dinucleoside 57 were synthesized (e.g.…”

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

“…This resulted in a fine precipitate which was collected by centrifugation and washed repeatedly with acetone. This product was shown by 1 H, 31 P, 13 C NMR and ESI-MS to be the sodium salt of the P 1 ,P 2 -diimidazolide of pyrophosphoric acid (7a). It was obtained in nearly quantitative yield and in high purity (>97% by 31 P NMR).…”

“…Using the above procedure, we also prepared the diimidazolides of monochloromethylene-bis-phophonate (7b), monofluoromethylene-bis-phosphonate (7c), and dichloromethylene-bisphosphonate (7d). As with 7a, these compounds were isolated in almost quantitative yields and high purity as the disodium salts and characterized by their 1 H, 31 P, 13 C, and MS spectra.…”

“…When the reaction was carried out with an excess of CDI (molar ratio 3 : 1), significantly simpler spectra were obtained, in which two intermediates gradually converted into the final reaction product, the bis-imidazolide 7a, represented by the singlet at -20.8 ppm (Fig. 2, B) To assign the structures of the intermediates we carried out the above reaction using CDI labeled with 13 C on the carbonyl group ( 13 C-CDI). We used the 2-bond 13 C-31 P coupling to assign the 31 P resonances of intermediates that contained the -P-O-13 C(O)-mixed anhydride groups.…”