Synthesis of Trifluoromethylated Purine Ribonucleotides and Their Evaluation as 19F NMR Probes.
J Org Chem
; 85(5): 3440-3453, 2020 03 06.
Article
em En
| MEDLINE
| ID: mdl-31994393
ABSTRACT
Protected guanosine and adenosine ribonucleosides and guanine nucleotides are readily functionalized with CF3 substituents within the nucleobase. Protected guanosine is trifluoromethylated at the C8 position under radical-generating conditions in up to 95% yield and guanosine 5'-oligophosphates in up to 35% yield. In the case of adenosine, the selectivity of trifluoromethylation depends heavily on the functional group protection strategy and leads to a set of CF3-modified nucleosides with different substitution patterns (C8, C2, or both) in up to 37% yield. Further transformations based on phosphorimidazolide chemistry afford various CF3-substituted mono- and dinucleoside oligophosphates in good yields. The utility of the trifluoromethylated nucleotides as probes for 19F NMR-based real-time enzymatic reaction monitoring is demonstrated with three different human nucleotide hydrolases (Fhit, DcpS, and cNIIIB). Substrate and product(s) resonances were sufficiently separated to enable effective tracking of each enzymatic activity of interest.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribonucleosídeos
/
Ribonucleotídeos
Limite:
Humans
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Polônia