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Synthesis of Analogues of Acyclic Nucleoside Diphosphates Containing a (Phosphonomethyl)phosphanyl Moiety and Studies of Their Phosphorylation
Author(s) -
Doláková Petra,
Dračínský Martin,
Fanfrlík Jindřich,
Holý Antonín
Publication year - 2009
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200800911
Subject(s) - chemistry , phosphinate , phosphonate , moiety , stereochemistry , nuclear magnetic resonance spectroscopy , nucleoside , phosphorylation , phosphate , medicinal chemistry , organic chemistry , biochemistry , fire retardant
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)