On the Discorhabdins Leading to the Aleutianamine Ring System: A One‐Step in Situ Transformation Characterized Through Computational and Experimental Studies and Its Implications on Biosynthesis, Synthesis, and Pharmacology
Year: 2026
Type: article
Abstract: ABSTRACT We disclose an efficient transformation of the relatively common pyrroloiminoquinone discorhabdin alkaloids from Alaskan Latrunculia spp. to the complex ring system of aleutianamine by an acid catalyzed process that mimics the proposed endogenous genesis from 3‐dihydrodienyl discorhabdin precursors. The azepine ring system is formed by a concerted 1,2‐alkyl shift of a proposed thiocarbenium‐iminium dication and this mechanism is supported by extensive density functional theory (DFT) analysis. Additional in vitro biological data further supports the aleutianamines as novel and highly potent inhibitors of multidrug resistant cancer lines exemplified further with cytotoxicity toward chemotherapy resistant chromophobe renal cell carcinoma (IC 50 = 130 nM). This report provides a key transformation that allows the incorporation of either synthetic or biosynthetic starting materials leading to the generation of the aleutianamine complex ring system in just a single step from the discorhabdin ring system.
DOI: 10.1002/anie.7864883
Institutions: Medical University of South Carolina, University of California, Davis, University of Hawaiʻi at Mānoa, Mayo Clinic, MUSC Hollings Cancer Center, National Oceanic and Atmospheric Administration, NOAA National Marine Fisheries Service Alaska Fisheries Science Center, NOAA National Marine Fisheries Service
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,510
OpenAlex ID: W7129048839