Aryl H-phosphonates. 10. Synthesis of nucleoside phosphoramidate and nucleoside phosphoramidothioate analogues via H-phosphonamidate intermediates

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Synthesis of a new type of dinucleoside monophosphate analogue with the 3′–5′ H-phosphonamidate internucleoside linkage, namely thymidin-3′-yl N(thymidin-5′-yl)-H-phosphonamidate 4, was achieved via the reaction of a suitably protected nucleoside aryl H-phosphonate with a 5′-amino-5′-deoxythymidine derivative. The usefulness of 4 as an intermediate for the preparation of various nucleotide analogues was assessed by converting it into the corresponding dinucleoside phosphoramidate and dinucleoside phosphoramidothioate derivatives bearing the PN bond in the bridging position of the phosphoramidate linkage.