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

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. (C) 1999 Elsevier Science Ltd. All rights reserved.