title: Prolinol-based nucleoside phosphonic acids: synthesis and properties.
abstract: Commercially available trans-4-hydroxy-L-proline has been used as a starting material for the synthesis of prolinol-based nucleotide analogues with N-phosphonomethyl moiety attached to the nitrogen atom of prolinol ring. The synthetic methodology based on the inversion of configuration at both 1- and 4- positions led, in result, to all diastereoisomeric O-protected 4-mesyloxyprolinol-N-methylphosphonates. Alkylation of nucleobases using the synthons afforded the nucleotide analogues corresponding to alpha- and beta-nucleotides in both L- and D-series. The NMR-based conformational study of alpha- and beta-nucleotides in aqueous solution performed at two different pH values securing either N-fully protonated or deprotonated forms revealed in both cases occurrence of the same mostly populated conformer. All final prolinol-based nucleoside phosphonic acids were tested for cytotoxic and antiviral properties, but no significant activity was found.
authors.affiliation: Institute of Organic Chemistry & Biochemistry, Acad. Sci., Flemingovo n. 2, 166 10 Prague 6, Czech Republic.
authors.forename: Václav
authors.initials: V
authors.lastname: Vanĕk
authors.forename: Milos
authors.initials: M
authors.lastname: Budĕsínský
authors.forename: Radek
authors.initials: R
authors.lastname: Liboska
authors.forename: Vladimíra
authors.initials: V
authors.lastname: Hurychová
authors.forename: Ivan
authors.initials: I
authors.lastname: Rosenberg
mesh_terms: D003854:Deoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009705:Nucleosides / Q000737:chemistry; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry*
chemical_list: D003854:Deoxyribonucleotides; D009705:Nucleosides; D063065:Organophosphonates; D011759:Pyrrolidines; C010509:prolinol