Prolinol-based nucleoside phosphonic acids: new isosteric conformationally flexible nucleotide analogues

Autor:	Ivan Rosenberg, Markéta Rinnová, Miloš Buděšínský, Václav Vaněk
Rok vydání:	2009
Předmět:	chemistry.chemical_classification Stereochemistry Organic Chemistry Synthon Alkylation Biochemistry Prolinol Nucleobase chemistry.chemical_compound chemistry Drug Discovery Moiety Nucleotide Nucleoside Conformational isomerism
Zdroj:	Tetrahedron. 65:862-876
ISSN:	0040-4020
DOI:	10.1016/j.tet.2008.11.035
Popis:	trans-4-Hydroxy- l -proline has been used as a starting material for the synthesis of prolinol-based nucleotide analogues with an N-phosphonomethyl moiety attached to the prolinol ring nitrogen atom. The synthetic methodology based on the inversion of configuration at both 1- and 4-position led to all diastereoisomeric O-protected 4-mesyloxyprolinol-N-phosphonates. Alkylation of nucleobases using the synthons in the l -series afforded the nucleotide analogues corresponding to α- l - and β- l -nucleotide. The NMR-based conformational study of these compounds in aqueous solution performed at two different pH values, showing either N-fully protonated or deprotonated forms, revealed the occurrence of the same mostly populated conformer in both cases. All final l -prolinol-based nucleoside phosphonic acids were tested for cytotoxic and antiviral properties, but no significant activity was found.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::f9f7676a460737733bc46e71bba1e898 https://doi.org/10.1016/j.tet.2008.11.035 Zobrazit plný text záznamu Full Text from ScienceDirect