10.1080/15257779408011881
The study presents a solution phase approach to synthesize phosphorylated dinucleotides, which are potentially useful therapeutic agents and important for studying weak interactions in molecular systems. The researchers developed nine or ten-step syntheses to produce the dimers dpApA, dApAp, dpTpT, and dTpTp in yields of 49%, 45%, 32%, and 20% respectively. The synthesis involves several key chemicals: nucleoside phosphines (4 and 5) react with protected nucleosides (6 or 7) to form fully protected dimers (8 and 9). These dimers are then selectively deprotected to yield dinucleotides with a deblocked 3'- or 5'-OH (10-13). A p-nitrophenethylphosphine derivative (14) is used to add a terminal phosphate group, leading to the formation of compounds (15-18). Further reactions, including oxidation and removal of protecting groups, result in the final phosphorylated dinucleotides (21, 22, 24, and 27). The synthetic intermediates were characterized by 1H and 31P NMR, and the structures of the final products were confirmed by hydrolysis with alkaline phosphatase and comparison with authentic samples.