161824-87-9Relevant academic research and scientific papers
Synthesis and conformational analysis of fluorinated uridine analogues provide insight into a neighbouring-group participation mechanism
Brown, Murray J. B.,Goss, Rebecca Jane Miriam,Lebl, Tomas,Michailidou, Freideriki,Sharma, Sunil Vishnuprasadji,Slawin, Alexandra M. Z.
, (2020)
Fluorinated nucleoside analogues have attracted much attention as anticancer and antiviral agents and as probes for enzymatic function. However, the lack of direct synthetic methods, especially for 2′,3′-dideoxy-2′,3′-difluoro nucleosides, hamper their practical utility. In order to design more efficient synthetic methods, a better understanding of the conformation and mechanism of formation of these molecules is important. Herein, we report the synthesis and conformational analysis of a 2′,3′-dideoxy-2′,3′-difluoro and a 2′-deoxy-2′-fluoro uridine derivative and provide an insight into the reaction mechanism. We suggest that the transformation most likely diverges from the SN 1 or SN 2 pathway, but instead operates via a neighbouring-group participation mechanism.
A Facile Route to Pyrimidine-Based Nucleoside Olefins: Application to the Synthesis of d4T (Stavudine)
Luzzio, Frederick A.,Menes, Michael E.
, p. 7267 - 7272 (2007/10/02)
An efficient synthetic route to nucleoside olefins in the uridine, cytidine, and thymidine series is described which utilizes the Garegg-Samuelsson iodine/triphenylphosphine/imidazole-promoted deoxygenation of the 2',3'-hydroxyl groups as the key step.Cyclopentadiene ketal protection was employed for all the nucleoside 2',3'-hydroxyls to facilitate blocking of the 5'-hydroxyl and the pyrimidine nitrogens with the benzyl or 4-methoxybenzyl (PMB) groups.Deblocking of the cyclopentylidene group followed by olefination of the resulting diols provided protected nucleoside olefins 18-20.Starting with 5-methyluridine 4 and utilizing the 4-methoxybenzyl group for 5',N3 protection, the overall scheme provided the anti-HIV compound d4T (1) after deprotection of the PMB groups.The dibenzylhypoxanthine nucleoside diol 17 derived from inosine gave either unreacted starting material or decomposition products under several sets of conditions.
