Bismethylene Triphosphate Nucleotides of Uridine 4-Phosphate
Analogues: A New Class of Anionic Pyrimidine Nucleotide
Analogues
Scott D. Taylor
Farzad Mirzaei
Stephen L. Bearne
10.1021/jo702249j.s002
https://acs.figshare.com/articles/journal_contribution/Bismethylene_Triphosphate_Nucleotides_of_Uridine_4_Phosphate_Analogues_A_New_Class_of_Anionic_Pyrimidine_Nucleotide_Analogues/2957185
Cytidine-5‘-triphosphate synthase (CTPS) catalyzes the formation of cytidine triphosphate (CTP) from
glutamine, uridine 5‘-triphosphate (UTP), and adenosine 5‘-triphosphate (ATP). This reaction proceeds
via formation of the high-energy intermediate UTP-4-phosphate (UTP-4-P). Stable analogues of UTP-4-P may be potent inhibitors of CTPS and useful as lead structures for the development of anticancer
and antiviral agents. Several bismethylene triphosphate (BMT) nucleotides of uridine 4-phosphate (U-4-P) analogues have been prepared. A key step was the selective methanolysis, with the aid of a tin
catalyst, of the 5‘ ester moiety of 2‘,3‘,5‘-tri-<i>O</i>-acetyl or tri-<i>O</i>-benzoyl U-4-P analogues. We believe this
represents the first general approach to the selective cleavage of 5‘ benzoyl esters in benzoylated
nucleosides. Mitsunobu coupling of these 5‘-deprotected U-4-P analogues to an unsymmetrical, protected
BMT bearing a free phosphonic acid moiety at one of the terminal positions gave fully protected BMT-U-4-P analogues. Global deprotection of these species was achieved using TMSBr followed by treatment
with NH<sub>4</sub>OH−MeOH or NH<sub>4</sub>OH−pyridine. The resulting BMT nucleotides represent a new class of
anionic pyrimidine nucleotide analogues.
2008-02-15 00:00:00
pyrimidine nucleotide analogues
CTPS
BMT
Several bismethylene triphosphate
NH 4OH
CTP
phosphonic acid moiety
ATP
Bismethylene Triphosphate Nucleotides
UTP