BIFUNCTIONAL ACYCLIC NUCLEOSIDE PHOSPHONATES:2.SYMMETRICAL 2-{[BIS(PHOSPHONO)METHOXY]METHYL}ETHYL DERIVATIVES OF PURINES AND PYRIMIDINES

摘要

Novel bisphosphonate alkylating agent,tetraisopropyl (2-[(mesyloxy)methyl]propane-l,3-diyl)bis(oxymethylene)bisphosphonate 19,was synthesized from diethyl 2,2-bis-(hydroxymethyl)malonate.Decarbethoxylation of the diethyl 2,2-dimethyl-l,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 N~1-substituted pyrimidines were converted to appropriate free bisphosphonic acids.No antiviral or cytostatic activity was detected.