Synthesis and properties of a novel phosphodiester analogue, nucleoside boranophosphorothioate

Synthesis of Boron-Containing ADP and GDP Analogues: Nucleoside 5′-(P-Boranodiphosphates)

“…However, distribution of charge Figure. Phosphate-modified nucleotides density and consequently the polarity of the modified P-moiety would differ as would the metal binding and selectivity. Furthermore, since the BH 3 group in boranophosphates is isoelectronic as well as isosteric with the CH 3 group, it might be expected that P-boronated nucleotides would also exhibit some desirable properties of the nucleoside methylphosphonates [19], such as increased lipophilicity and resistance to nucleases [10] [14]. Additionally, P-boronated nucleotides may offer a unique advantage over other modified congeners because the former can be used for boron neutron-capture therapy (BNCT) [20], a radiation therapy that can selectively destroy cells that have preferentially taken up boron.…”

“…Based on our previous studies showing that boranophosphates are more lipophilic than natural phosphates [14], the introduction of BH 3 at P(a) or P(b) of nucleoside diphosphates is likely to enhance their lipophilicity and assist in their crossing the plasma membrane while maintaining the negative charge of the phosphate. The BH 3 group in an NDPaB is expected to form neither classical H-bonds nor coordinate metal ions as well as the O-atom in the parental ADP and GDP.…”

“…The BH 3 group in an NDPaB is expected to form neither classical H-bonds nor coordinate metal ions as well as the O-atom in the parental ADP and GDP. Thus, the novel combination of high lipophilicity, reasonable water solubility, and nuclease resistance could be extremely useful for drug design [14].…”

Synthesis of a novel triphosphate analogue: nucleoside α-P-borano, α-P-thiotriphosphate

“…1,2 Yet once in DNA or RNA, the phosphorothioate 3 and boranophosphate 4 linkages are more resistant to exo-and endo-nucleases than normal phosphate diesters. By structurally combining the phosphorothioate [S-PNO] 2 and boranophosphate [ONP-BH 3 ] 2 , we recently reported the first example of a boranothiophosphate moiety [SNP-BH 3 ] 2 , dithymidine boranphosphorothioate, 5 which is stable from pH 3 to 11 and is a more nuclease resistant and highly lipophilic phosphodiester analogue of DNA. We expected that the corresponding NTP analogue, nucleoside [a-borano, athio]triphosphate (Fig.…”

Synthesis and characterization of the novel l‐(substituted phenoxy/phenyl)‐2‐phospholene and phospholane 1‐oxide derivatives

“…In recent years focus is increased on the synthesis of bioactive phosphorus compounds [3], among those, phospha sugars are interesting due to their potential biological activities in various fields [4]. In view of their characteristic biological activities, nitro-and/or chloro-substituted phenyl phospha sugar derivatives are expected to have heightened bioactivity.…”