The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• 2-chloro-9-(β-D-arabinofuranosyl)adenine (6) in 45 min, the formation of 2-chloro-9-(β-D-xylofuranosyl)adenine (7) proceeded very slowly attaining ca. 8% yield in 48 h. Keywords: chemoenzymatic synthesis; clofarabine; nucleoside phosphorylases; phosphopentomutase; recombinant E. coli ribokinase

• using the α-D-pentofuranose-1-phosphates as glycosylating agents. The cascade synthesis involves a sequential conversion of D-pentoses into their 5-monophosphates catalyzed by the recombinant E. coli ribokinase (RK; ATP co-factor) [27], stereospecific isomerization of the 5-phosphates into α-D

• D-pentoses into nucleosides of 2-chloroadenine catalyzed by the recombinant E. coli ribokinase (RK), phosphopentomutase (PPM) and purine nucleoside phosphorylase (PNP) (purine numbering was used throughout of the manuscript). The structures of 1-phosphates of α-D-arabinofuranose (13a; AraFur-1P) and