1010804-55-3Relevant academic research and scientific papers
Bismethylene triphosphate nucleotides of uridine 4-phosphate analogues: A new class of anionic pyrimidine nucleotide analogues
Taylor, Scott D.,Mirzaei, Farzad,Bearne, Stephen L.
, p. 1403 - 1412 (2008/09/17)
(Chemical Equation Presented) 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-O-acetyl or tri-O-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 NH4OH-MeOH or NH 4OH-pyridine. The resulting BMT nucleotides represent a new class of anionic pyrimidine nucleotide analogues.
