Straightforward Synthesis of Labeled and Unlabeled Pyrimidine d4Ns via 2′,3′ ‐ Diyne seco Analogues through Olefin Metathesis Reactions

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)