Tadashi Araki

Chemo-enzymatic synthesis of 2′,3′-dideoxy-3′-fluoro-β-d-guanosine via 2,3-dideoxy-3-fluoro-α-d-ribose 1-phosphate

Abstract 2,3-Dideoxy-3-fluoro-α- d -ribose 1-phosphate 2 was stereoselectively synthesized and converted to 2′,3′-dideoxy-3-fluoro-β- d -guanosine 1 by enzymatic reaction using purine nucleoside phosphorylase. This chemo-enzymatic strategy was first applied to the synthesis of 1 .

Efficient chemo-enzymatic syntheses of pharmaceutically useful unnatural 2'-deoxynucleosides.

Our chemo-enzymatic method was successfully applied to the synthesis of 2-chloro-2′-deoxyadenosine (CdA, cladribine) in two ways: 1) direct conversion of chemically synthesized 2-deoxy-α-D-ribose 1-phosphate (dRP) to CdA; 2) a two-step route via 9-(2-deoxy-β-D-ribos-1-yl)-2,6-dichloropurine (Cl2Pu-dR, 5).