Collect. Czech. Chem. Commun.
2007, 72, 965-983
https://doi.org/10.1135/cccc20070965
Bifunctional Acyclic Nucleoside Phosphonates: 2. Symmetrical 2-{[Bis(phosphono)methoxy]methyl}ethyl Derivatives of Purines and Pyrimidines
Silvie Vrbková*, Martin Dračínský and Antonín Holý
Centre for New Antivirals and Antineoplastics, Gilead Sciences & IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
Abstract
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). N9-Substituted purines and N1-substituted pyrimidines were converted to appropriate free bisphosphonic acids. No antiviral or cytostatic activity was detected.
Keywords: Acyclic nucleoside phosphonates; ANPs; Acyclic nucleotide analogues; Phosphonomethyl ethers; Adefovir; Bisphosphonates; Nucleobases.
References: 25 live references.
