Synthesis and NMR conformational studies of stable analogues of 2-deoxy-α-D-ribose-1-phosphate

Abstract

Malonate ethers and phosphonate derivatives of 2-deoxyribose and 2-deoxy-2-fluoroarabinose have been synthesized, for the first time, as stable analogues of 2-deoxy-α- d-ribose-1-phosphate ( 1). In almost all the cases, the α-anomers have been obtained as the major isomers. The NMR conformational analysis performed indicate a similar conformational equilibria for the natural phosphate 1 and the here described analogues, with the exception of the glycosyl phosphonate 3α. None of the compounds were inhibitory to purified E. coli thymidine phosphorylase at 250 μM. Also, when administered to intact CEM cells, no inhibitory effect was observed in hypoxanthine and inosine metabolising enzymes, including purine nucleoside phosphorylase.