Next-Generation Total Synthesis of Vancomycin.

ABSTRACT: A next-generation total synthesis of vancomycin aglycon is detailed that was achieved in 17 steps (longest linear sequence, LLS) from the constituent amino acid subunits with kinetically controlled diastereoselective introduction of all three elements of atropisomerism. In addition to new syntheses of three of the seven amino acid subunits, highlights of the approach include a ligand-controlled atroposelective one-pot Miyaura borylation-Suzuki coupling sequence for introduction of the AB biaryl axis of chirality (>20:1 dr), an essentially instantaneous and scalable macrolactamization of the AB ring system nearly free of competitive epimerization (>30:1 dr), and two room-temperature atroposelective intramolecular S_NAr cyclizations for sequential CD (8:1 dr) and DE ring closures (

SUBMITTER: Moore MJ 

PROVIDER: S-EPMC7501256 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature