Synthesis of Analogues of Acyclic Nucleoside Diphosphates Containing a (Phosphonomethyl)phosphanyl Moiety and Studies of Their Phosphorylation

✍ Scribed by Petra Doláková; Martin Dračínský; Jindřich Fanfrlík; Antonín Holý

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 265 KB
• Volume: 2009
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.200800911

✦ Synopsis

Abstract

Acyclic nucleoside diphosphonate derivatives of purines and pyrimidines were prepared by Mitsunobu reaction of suitably protected heterocyclic bases with alcohols containing the (phosphonomethyl)phosphanyl moiety. Furthermore, nonhydrolyzable acyclic analogues of dUDP were prepared as potential inhibitors of dUTPase. Their phosphorylation to analogues of dUTP, however, gave mixtures of linear and branched phosphates. The courses of the phosphorylation reactions were followed by ^31^P NMR spectroscopy, and we discovered that both phosphonate and phosphinate moieties react with 1,1′‐carbonyldiimidazole and tri‐n‐butylammonium phosphate. The p__K__~a~ values of the (phosphonomethyl)phosphanyl system were also determined by ^31^P NMR spectroscopy (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)