Biomimetic Total Synthesis of the Spiroindimicin Family of Natural Products

A unified strategy for the biomimetic total synthesis of the spiroindimicin family of natural products was reported. Key transformations include a one‐pot two‐enzyme‐catalyzed oxidative dimerization of L‐tryptophan/5‐chloro‐L‐tryptophan to afford the bis‐indole precursors chromopyrrolic acid/5′,5′′‐dichloro‐chromopyrrolic acid, and regioselective C3′−C2′′ and C3′−C4′′ bond formation converting a common bis‐indole skeleton to two skeletally different natural products, including (±)‐spiroindimicins D and G with a [5,5] spiro‐ring skeleton, and (±)‐spiroindimicins A and H with a [5,6] spiro‐ring skeleton, respectively. The total synthesis of the spiroindimicin family of natural products with both [5,5] and [5,6] spiro‐ring skeletons was achieved via a biomimetic “dimerize‐and‐divert” strategy. A biocatalytic process for the oxidative dimerization of L‐tryptophan was developed for the preparation of a bis‐indole intermediate, which was converted to spiroindimicins via regioselective oxidative C3′−C2′′ and C3′−C4′′ couplings.