Nucleoside reverse transcriptase inhibitors are the only drugs so far approved for the treatment of AIDS. Several nucleoside analogs are potent inhibitors of human immunodeficiency virus(HIV) in cell culture. However,...Nucleoside reverse transcriptase inhibitors are the only drugs so far approved for the treatment of AIDS. Several nucleoside analogs are potent inhibitors of human immunodeficiency virus(HIV) in cell culture. However, in many cases the nucleoside derivatives have a poor affinity for nucleoside kinases. Nucleoside 5′-phosphorothioates is relatively resistant to enzymatic transformations. In this paper, 2′,3′-O-alkoxymethylidene adenosine 5′-thiophosphoramidates were synthesized through a highly efficient approach. The new compounds were characterized by NMR, IR and ESI-MS.展开更多
Phosphoramidates of nucleosides are continuing to be an important class of rationally designed therapeutics especially as oligonucleotide analogs employed as antisense and antigene agents. A series of different nucleo...Phosphoramidates of nucleosides are continuing to be an important class of rationally designed therapeutics especially as oligonucleotide analogs employed as antisense and antigene agents. A series of different nucleoside 5’-thiophosphoramidates have recently been synthesized, their electrospray ionization mass specra have been investigated. The positive and negative electrospray ionization mass spectra all gave strong pseudomolecular ions and characteristic fragment ions, however, they showed different fragmentation pathways. In the negative ion MS, the deprotonated molecule showed the base peak with loss of propylene. In the positive ion MS, the protonated molecule usually produced ions from loss of water, amino acid methyl ester, methyl alcohol, uridine and phosphoryl group. These mass spectral fragmentation pathways are helpful to determination of similarphosphoramidates of nucleosides.展开更多
文摘Nucleoside reverse transcriptase inhibitors are the only drugs so far approved for the treatment of AIDS. Several nucleoside analogs are potent inhibitors of human immunodeficiency virus(HIV) in cell culture. However, in many cases the nucleoside derivatives have a poor affinity for nucleoside kinases. Nucleoside 5′-phosphorothioates is relatively resistant to enzymatic transformations. In this paper, 2′,3′-O-alkoxymethylidene adenosine 5′-thiophosphoramidates were synthesized through a highly efficient approach. The new compounds were characterized by NMR, IR and ESI-MS.
文摘Phosphoramidates of nucleosides are continuing to be an important class of rationally designed therapeutics especially as oligonucleotide analogs employed as antisense and antigene agents. A series of different nucleoside 5’-thiophosphoramidates have recently been synthesized, their electrospray ionization mass specra have been investigated. The positive and negative electrospray ionization mass spectra all gave strong pseudomolecular ions and characteristic fragment ions, however, they showed different fragmentation pathways. In the negative ion MS, the deprotonated molecule showed the base peak with loss of propylene. In the positive ion MS, the protonated molecule usually produced ions from loss of water, amino acid methyl ester, methyl alcohol, uridine and phosphoryl group. These mass spectral fragmentation pathways are helpful to determination of similarphosphoramidates of nucleosides.
