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Straightforward Synthesis of Labeled and Unlabeled Pyrimidine d4Ns via 2′,3′ ‐ Diyne seco Analogues through Olefin Metathesis Reactions
Author(s) -
Gillaizeau Isabelle,
Lagoja Irene M.,
Nolan Steve P.,
Aucagne Vincent,
Rozenski Jef,
Herdewijn Piet,
Agrofoglio Luigi A.
Publication year - 2003
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.200390107
Subject(s) - chemistry , ring closing metathesis , pyrimidine , moiety , metathesis , nucleoside , ruthenium , stereochemistry , combinatorial chemistry , olefin metathesis , ribose , salt metathesis reaction , acyclic diene metathesis , catalysis , organic chemistry , polymerization , enzyme , polymer
The synthesis of dideoxynucleosides (ddNs) or didehydro‐dideoxynucleosides (d4Ns) from nucleosides has been extensively reviewed. While previously described methods are based on the modification of the 2′‐ and/or 3′‐OH group of the intact ribose moiety, the use of a ring‐closing metathesis (RCM) for the formation of the unsaturated cyclic system of nucleosides could be a straightforward approach to the d4Ns. Thus, as part of our drug labeling program, this paper reports a straightforward synthesis of 2′,3′‐didehydro‐2′,3′‐dideoxyuridine (d4U) and [1′,2′,3′,4′,5′‐ 13 C 5 ,6‐ 13 C,1,3‐ 15 N 2 ]d4T using the RCM protocol. This paper discusses the preparation of nucleoside dienes and the activity of ruthenium‐based metathesis catalysts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)