Prolinol-based nucleoside phosphonic acids: synthesis and properties.
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.
Vanĕk
Václav
V
Institute of Organic Chemistry & Biochemistry, Acad. Sci., Flemingovo n. 2, 166 10 Prague 6, Czech Republic.
Budĕsínský
Milos
M
Liboska
Radek
R
Hurychová
Vladimíra
V
Rosenberg
Ivan
I
D003854:Deoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009705:Nucleosides / Q000737:chemistry; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry*
D003854:Deoxyribonucleotides; D009705:Nucleosides; D063065:Organophosphonates; D011759:Pyrrolidines; C010509:prolinol