SYNTHESIS AND NMR CONFORMATIONAL STUDIES OF STABLE ANALOGS OF 2-DEOXY-ALPHA-D-RIBOSE-1-PHOSPHATE

Malonate ethers and phosphonate derivatives of 2-deoxyribose and 2-deo xy-2-fluoroarabinose have been synthesized, for the first time, as sta ble analogues of 2-deoxy-alpha-D-ribose-1-phosphate (1). In almost all the cases, the alpha-anomers have been obtained as the major isomers. The NMR conformational analysis performed indicate a similar conforma tional equilibria for the natural phosphate P and the here described a nalogues, with the exception of the glycosyl phosphonate 3 alpha. None of the compounds were inhibitory to purified E. coli thymidine phosph orylase at 250 mu M. Also, when administered to intact CEM cells, no i nhibitory effect was observed in hypoxanthine and inosine metabolising enzymes, including purine nucleoside phosphorylase. (C) 1998 Elsevier Science Ltd. All rights reserved.