Synthesis, structure and reactions of uridine 2′-C,3′-O-γ-butyrolactone: versatile intermediate for the synthesis of 2′-C-branched nucleosides

Abstract

Uridine 2′-C-3′-O-γ-butyrolactone 5a has been prepared by cyclisation of 2′-α-C-carboxymethyl-2′-deoxyuridine 8 in acetic acid–methanol. Detailed ¹H NMR studies on compound 5a clearly demonstrate cis fusion between the γ-lactone and the sugar moiety, and determination of conformationally averaged structural descriptors, i.e. the pseudorotation phase angle and the puckering amplitude, suggests that the dominant conformer of the furanose ring is S. The 2′-C,3′-O-lactone 5a and its 5′-protected derivatives (5b and 5c) readily undergo aminolyses to yield a range of amide derivatives. Reaction with 5′-amino-5′-deoxythymidine gave a 2′–5′-amide-linked analogue of a dinucleoside monophosphate. Under acidic conditions the amides slowly relactonised. The 5′-protected lactones were also shown to react with simple organometallic reagents.

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