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′-13C5,6-13C,1,3-15N2]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)