A Chemo-Enzymatic Synthesis of β-d-Arabinofuranosyl Purine Nucleosides

Abstract

4.02 br. m 3.63 dd / 4.12 dd J 5,4 = 2.12 J 5',4 = 1.10 gem J 5,5' = 12.82 3.04 J P,H1 = 6.90 J P,H2 = 1.74 5.50 dd J 1,2 = 4.70 4.18 m J 2,3 = 3.40 3.93 m J 3,4 1.0 4.19 m 3.83 dd / 3.71 dd J 5,4 = 3.36 J 5',4 = 5.96 gem J 5,5' = 12.28 2.49 J P,H1 = 5.18 J P,H2 < 1.0 -D-Ribofuranose 5.63 dd J 1,2 = 5.55 4.04 dd J 2,3 = 5.96 4.09 q J 3,4 = 4.15 4.21 dt 3.78 br.dd / 3.66 br.dd 3.03 J P,H1 = 4.30 J P,H2 < 1.0

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

“…The structures of the α- and β-anomers 12a and 12b were verified by a careful analysis of the 1 H and 13 C NMR spectra {[ 1 H, 1 H] and [ 1 H, 13 C] 2D COSY and NOESY spectra} as well as by the 19 F and 31 P NMR and by comparison with published 1 H and 13 C NMR data for the α-anomer 12a [19] and the closely related D-arabinofuranose-1-phosphates [22,32] (Tables S1 and S2 in Supporting Information File 1). It is noteworthy that 1,2,3,5-tetra- O -acetyl-D-arabinofuranose and 1- O -acetyl-2,3,5-tri- O -benzoyl-D-arabinofuranose were shown to transform in a mixture of 1-phosphates of β-D-arabinopyranose ( 13b ; Ara Pyr -1P; major isomer) and α-D-arabinofuranose ( 13a ; Ara Fur -1P; minor isomer) under MacDonald reaction conditions (Fig.…”

“…Recently, we have studied the synthesis of purine and pyrimidine β-D-arabinofuranosides by using α-D-arabinofuranose-1-phosphate (Ara-1P) as the glycosylating agent and the respective recombinant E. coli nucleoside phosphorylases as biocatalysts [22–23]. It was thus shown that Ara-1P is a universal glycosylating substrate for the synthesis of both purine and pyrimidine nucleosides.…”

“…In turn, the MacDonald method, originally proposed by the author for the synthesis of D-hexopyranose-1-phosphates [29–31], was used for obtaining Ara-1P. The method comprised the treatment of 1,2,3,5-tetra- O -acetyl-D-arabinofuranose or 1- O -acetyl-2,3,5-tri- O -benzoyl-D-arabinofuranose with anhydrous phosphoric acid followed by the deprotection with LiOH [22]. A similar approach was studied in the present work for the synthesis of purine and pyrimidine 2-deoxy-2-fluoro-β-D-arabinofuranosides.…”

“…It is noteworthy that 1,2,3,5-tetra- O -acetyl-D-arabinofuranose and 1- O -acetyl-2,3,5-tri- O -benzoyl-D-arabinofuranose were shown to transform in a mixture of 1-phosphates of β-D-arabinopyranose ( 13b ; Ara Pyr -1P; major isomer) and α-D-arabinofuranose ( 13a ; Ara Fur -1P; minor isomer) under MacDonald reaction conditions (Fig. 2) [22]. On the contrary, the α- and β-anomers 12a and 12b are the main products in a ratio of ca.…”

“…Previously, we have applied the MacDonald method for the synthesis of α-D-arabinofuranose-1-phosphate (Ara-1P) and showed that it is a versatile substrate for the enzymatic synthesis of both purine and pyrimidine nucleosides [22–23]. In addition, we demonstrated that D-ribose and 2-deoxy-D-ribose can be converted to nucleosides in the cascade one-pot synthesis under the consecutive action of three E. coli enzymes, i.e., ribokinase (RK), phosphopentomutase (PPM) and nucleoside phosphorylases [24–27] (for a recent review, see [28]).…”