Facile Hydrogen-Deuterium Exchange at the 5′-Position of an Analogue of S-Adenosyl-l-methionine

S-3′,4′-anhydroadenosyl-l-methionine is an analogue of the S-adenosyl-l-methionine coenzyme. Here we report on a rapid solvent exchange of the methylene protons at the 5′-position of this analogue. The rate of H/D exchange was measured by nuclear magnetic resonance spectroscopy under buffered conditions in deuterium oxide. The reaction is specific base catalyzed and displays a second-order rate constant of 2 × 104 M−1 s−1, which corresponds to a rate enhancement of 1012 compared to solvent exchange of α-methylene protons in acyclic, aliphatic sulfonium ions. No other carbon bonded hydrogens in the molecule exchange with solvent under the experimental conditions. Allylic stabilization of a carbanionic-like transition state for the solvent exchange process can account for these results. Solvent exchange under these mild conditions provides a simple way to prepare a 5′-2H-labeled form of the coenzyme analogue.