Chemoenzymatic synthesis of Park’s nucleotide: toward the development of high-throughput screening for MraY inhibitors

An efficient chemoenzymatic synthesis of UDP-N-acetylmuramyl-l-alanyl-γ-d-glutamyl-meso-diaminopimelyl-d-alanyl-d-alanine (Park’s nucleotide) is reported. UDP-MurNAc is efficiently synthesized by a minimum number of protecting strategies. One-pot amino acid ligation reactions catalyzed by MurC, D, E, and F enzymes are amenable to scale-up production.