Biosynthetic pathways often rely on enzymes to append hydroxyl and thiol groups in specific locations on an already-assembled complex molecular framework, thereby preventing interference from these reactive groups at earlier stages. Inspired by this propensity, Kim et al. (p. 238; see the Perspective by Miller) adopted an analogous strategy in chemical synthesis of the fungal metabolite (+)-ll,ll'-dideoxyverticillin A, a dimer of alanine-tryptophan dipeptide derivatives with a sensitive bridging disulfide motif. The authors prepared the dimer framework first, and then relied on its stereochemistry to direct the simultaneous introduction of four OH groups using an experimentally optimized oxidant. The next step stereoselectively replaced all four hydroxyls with sulfur, yielding an intermediate that was easily oxidized to the final product. The efficient 10-step synthesis yielded sufficient product for crystallo-graphic characterization.
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