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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