Bismethylene triphosphate nucleotides of uridine 4-phosphate analogues: a new class of anionic pyrimidine nucleotide analogues

The Journal of Organic Chemistry
S D TaylorStephen L Bearne

Abstract

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 NH4OH-pyridine. The resulting BMT nucleotides represent a new class of anionic pyrimidine nucleotide analogues.

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Citations

Apr 29, 2010·Chemical Communications : Chem Comm·Srinath ThirumalairajanStephen L Bearne
Aug 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·G K Surya PrakashGeorge A Olah
Nov 2, 2013·Chemical Communications : Chem Comm·Natsuhisa OkaKaori Ando
Dec 13, 2019·The Analyst·Zhancun BianZhongyu Wu
Apr 23, 2009·Chemical Reviews·K C Kumara SwamyK V P Pavan Kumar
Jun 22, 2011·The Journal of Organic Chemistry·Samy Mohamady, Scott D Taylor
Mar 9, 2019·Organic Letters·Marine GavelThomas Lecourt
Dec 19, 2017·Journal of the American Chemical Society·Chun Pong TamJack W Szostak
May 15, 2015·Organic Letters·Anastasia P KadinaCharles E McKenna

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