Total Syntheses of Diketopiperazine Alkaloids via Divergent C3–N1' and C3–C5' Bond Anchor

Abstract Diketopiperazine alkaloids are typically soldered via an inner tryptophan–tryptophan linkage diversely from C3–carbon/nitrogen anchor. The manifold stereochemical frameworks afford broad spectrum of pharmacological activities, meanwhile pose formidable challenges for the efficient synthesis of these alkaloids, particularly in addressing chemoselectivity, regioselectivity, and stereoselectivity. Herein, we disclosed a divergent oxidative coupling between designed 8 and aniline derivatives 13 via the steerable iodine‐releasing reagent 14 , achieving the divergent total syntheses of diketopiperazine alkaloids via C3–N1' and C3–C5' bond anchor. The electronic and steric attributes from aniline govern chemo‐ and site‐selectivity for the linkage, enabling programmable assembly for divergently anchored alkaloids libraries. This approach established a stereospecific platform for the unified synthesis of three bioactive alkaloids via a dominant endo ‐selective manifold: (+)‐tetratryptomycin B, (+)‐pestalazine B, and (+)‐ iso ‐naseseazine B. The aniline‐regulated paradigm unlocked cross‐coupling with predictable selectivity for C3‐centered alkaloid syntheses.