SYNTHESIS, STRUCTURE AND REACTIONS OF URIDINE 2'-C,3'-O-GAMMA-BUTYROLACTONE - VERSATILE INTERMEDIATE FOR THE SYNTHESIS OF 2'-C-BRANCHED NUCLEOSIDES

Uridine 2'-C-3'-O-gamma-butyrolactone 5a has been prepared by cyclisat ion of 2'-alpha-C-carboxymethyl-2'-deoxyuridine 8 in acetic acid-metha nol, Detailed H-1 NMR studies on compound 5a clearly demonstrate cis f usion between the gamma-lactone and the sugar moiety, and determinatio n of conformationally averaged structural descriptors, i.e. the pseudo rotation phase angle and the puckering amplitude, suggests that the do minant conformer of the furanose ring is S, The 2'-C,3'-O-lactone 5a a nd its 5'-protected derivatives (5b and 5c) readily undergo aminolyses to yield a range of amide derivatives, Reaction with 5'-amino-5'-deox ythymidine gave a 2'-5'-amide-linked analogue of a dinucleoside monoph osphate. Under acidic conditions the amides slowly relactonised, The 5 '-protected lactones were also shown to react with simple organometall ic reagents.