A Streamlined Synthesis of Adenosine Vinylsulfonamide Probes for Aminoacyl‐AMP Mimicry in NRPS

-mediated Horner reaction performed near 0°C, enabling highly diastereoselective AVS formation with minimal epimerization under mild, open-air conditions. The method tolerates diverse amino acid-derived substrates, including electron-rich L-Tyr derivatives relevant to tetrahydroisoquinoline alkaloid biosynthesis. Functional evaluation by LC-MS/MS confirmed covalent capture of the NRPS SfmC by an L-Tyr-derived probe, demonstrating that AVS constructs prepared by this route retain full biochemical competence. This streamlined synthesis enhances reliable access to stereochemically well-defined AVS probes and supports structural and mechanistic studies across diverse NRPS systems.