Bifunctional acyclic nucleoside phosphonates: 2. Symmetrical 2-{[bis(phosphono)methoxy]methyl}ethyl derivatives of purines and pyrimidines

Article abstract of DOI:10.1135/cccc20070965

Novel bisphosphonate alkylating agent, tetraisopropyl (2-[(mesyloxy)methyl] propane-1,3-diyl]bis(oxymethylene)bisphosphonate 19, was synthesized from diethyl 2,2-bis-(hydroxymethyl)malonate. Decarbethoxylation of the diethyl 2,2-dimethyl-1,3-dioxane-5,5-dicarboxylate was followed by chloromethylation of 2-[(benzyloxy)methyl]propane-1,3-diol and Arbuzov reaction with triisopropyl phosphite. Bisphosphonate building block 19 was used in the alkylation of various nucleobases (2-amino-6-chloropurine, adenine, 2-amino-6-(cyclopropyl) aminopurine, cytosine, uracil and 4-methoxy-5-methylpyrimidin-2(1H)-one). N ⁹-Substituted purines and N¹-substituted pyrimidines were converted to appropriate free bisphosphonic acids. No antiviral or cytostatic activity was detected.