Abstract
Methanobactin OB3b (Mbn-OB3b) is a unique natural product featuring two ene-thiolate-azlactone rings incorporated in a rigidified peptide backbone. The stunning affinity of this chalkophore for copper (Ka ≈ Cu(I) 10E34) makes it a prominent lead compound for Cu-transport, metabolism, and detoxification. Its exceptional structure poses particular challenges for biosynthesis and chemical manipulation. Here, we report the first total synthesis of Cu(I)-bounded methanobactin OB3b featuring as key transformations a cyclodehydration-thioacylation sequence, to generate the conjugated heterocyclic systems, and a copper-templated cyclization, to complete the caged structure of the sensitive chalkophore.
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Supplementary material

Supporting Information
Additional Figures and Experimental Procedures

Spectra Collection
Copies of NMR spectra