Abstract
In the present work, we suggested anion exchange resins in the phosphate form as a source of phosphate, one of the substrates of the phosphorolysis of uridine, thymidine, and 1-(β-ᴅ-arabinofuranosyl)uracil (Ara-U) catalyzed by recombinant E. coli uridine (UP) and thymidine (TP) phosphorylases. α-ᴅ-Pentofuranose-1-phosphates (PF-1Pis) obtained by phosphorolysis were used in the enzymatic synthesis of nucleosides. It was found that phosphorolysis of uridine, thymidine, and Ara-U in the presence of Dowex® 1X8 (phosphate; Dowex-nPi) proceeded smoothly in the presence of magnesium cations in water at 20–50 °C for 54–96 h giving rise to quantitative formation of the corresponding pyrimidine bases and PF-1Pis. The resulting PF-1Pis can be used in three routes: (1) preparation of barium salts of PF-1Pis, (2) synthesis of nucleosides by reacting the crude PF-1Pi with an heterocyclic base, and (3) synthesis of nucleosides by reacting the ionically bound PF-1Pi to the resin with an heterocyclic base. These three approaches were tested in the synthesis of nelarabine, kinetin riboside, and cladribine with good to excellent yields (52–93%).
Highlights
Diverse variants of enzymatic syntheses of nucleosides using nucleoside phosphorylases as biocatalysts have been repeatedly described in original studies and discussed in a number of recent reviews
With this aim in view, studies have initiated on the synthesis of Rib-1Pi, dRib-1Pi, and Ara-1Pi based on the corresponding pyrimidine nucleosides and E. coli uridine phosphorylase (UP) and thymidine phosphorylase (TP) in the presence of Dowex® 1X8 in phosphate form (100–200 mesh; DowexnPi) as a source of inorganic phosphate in water instead of phosphate buffer
In order to find optimal conditions for the phosphorolysis reaction in the presence of Dowex-nPi, we analyzed some of the results of previous studies in terms of the role of the amount of Scheme 1: General scheme of the suggested synthesis of nucleosides employing the enzymatic phosphorolysis of pyrimidine nucleosides by recombinant E. coli uridine (UP) and thymidine (TP) phosphorylases to prepare the relevant α-ᴅ-pentofuranose-1-phosphates (PF-1Pis) and the use of them as either crude product, barium salt, or ionically bound by the resin in the enzymatic syntheses of nucleosides
Summary
Diverse variants of enzymatic syntheses of nucleosides using nucleoside phosphorylases as biocatalysts have been repeatedly described in original studies and discussed in a number of recent reviews (see, e.g., [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]).
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