A novel series of phenoxy C1-phosphonamidate derivatives of 2-deoxy-D-ribose have been synthesised as stable analogues of 2-deoxy-alpha-n-ribose-1-phosphate. A number of synthetic routes were explored for the preparation of these targets. The successful approach involved the synthesis of a protected C1-phosphonate ester 17 via Michaelis Arbuzov reaction, which was then hydrolysed and coupled with different amino acid esters using aldrithiol. Subsequent hydrogenolysis afforded the targets 2a-g, which were isolated as a mixture of diastereoisomers. The compounds were assayed for inhibition of thymidine phosphorylase (TP) and uridine phosphorylase (UP) and for antiviral and cytostatic activity. (C) 2013 Elsevier Ltd. All rights reserved.