17331-67-8Relevant articles and documents
PREPARATION OF 5'-O-PHOSPHONYLMETHYL ANALOGUES OF NUCLEOSIDE-5'-PHOSPHATES, 5'-DIPHOSPHATES AND 5'-TRIPHOSPHATES
Holy, Antonin,Rosenberg, Ivan
, p. 3447 - 3463 (2007/10/02)
Reaction of a trialkyl phosphite (VI) or sodium salt of dialkyl phosphite (V) with bromomethyl acetate afforded dialkyl acetoxymethanephosphonates VII which were alcoholyzed to dialkyl hydroxymethanephosphonates VIII.Tosylation of the compounds VIII gave dialkyl p-toluenesulfonyloxymethanephosphonates IX which on reaction with 2',3'-O-isopropylideneribonucleosides (I), 2',3'-O-ethoxymethyleneribonucleosides (XI) or 3'-O-tetrahydropyranyl-2'-deoxyribonucleosides in the presence of sodium hydride, followed by acid hydrolysis, were converted into alkyl esters of 5'-O-phosphonylmethylnucleosides XII.Treatment of compounds XII with trimethylsilyl iodide led to 5'-O-phosphonylmethylnucleosides II and XIV.The ribo derivatives II were also obtained in low yields by reaction of compounds I with sodium chloromethanephosphonate in the presence of sodium hydride.Compound II reacted with morpholine in the presence of N,N'-dicyclohexylcarbodiimide to give morpholides XV which on treatment with phosphate afforded 5'-O-phosphorylphosphonylmethylribonucleosides XVI.Analogously, 5'-O-diphosphorylphosphonylmethylribonucleosides XVII were obtained from the derivatives XV by reaction with diphosphate.The compounds II are resistant towards E. coli alkaline phosphomonoesterase and snake venom and bull semen 5'-nucleotidase.E. coli alkaline phosphomonoesterase degrades the compounds XVI and XVII to compounds II and inorganic phosphate.