Synthesis of nucleoside-amino acid conjugates containing boranephosphate, boranephosphorothioate and boranephosphoramidate linkages

Conjugates of 3^′-azido-2^′,3^′-dideoxythymidine (AZT) and 2^′,3^′-didehydro-2^′,3^′-dideoxythymidine (D4T) with the hydroxyl group of tyrosine containing boranephosphate and boranephosphorothioate moieties were prepared via the oxathiaphospholane and dithiaphospholane methodology as a mixture of P-diastereomers. Their structures were confirmed by MS analysis and ¹H, ³¹P NMR spectroscopy. It has been shown that the boranephosphorothioate linkage is unstable under acidic conditions. The first nucleoside-alanine conjugates connected through a boranephosphoramidate linkage were also obtained.