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Updated: Jan 16, 2026

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Total Syntheses of Giraldine I and Heterophyllisine
Chuang Li1, Fei Lu1, Ningwei Wang1
1Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Abstract:
Aconitine and related norditerpenoid alkaloids are chemically and biologically significant natural products that represent a formidable synthetic challenge. Here, we report the first total syntheses of aconitine-type alkaloid giraldine I and lactone-type alkaloid heterophyllisine. Key strategies include (1) early stage installation of the C4 all-carbon quaternary stereocenter and nitrogen atom via allene hydrocyanation, (2) skeletal editing through hydrodealkenylative fragmentation/Mannich cyclization to build the A/B/E/F tetracyclic scaffold, (3) a Claisen rearrangement/ring-closing metathesis (RCM) sequence followed by transannular pinacol coupling to form the characteristic C/D rings of aconitines, and (4) a bioinspired and regioselective Baeyer-Villiger oxidation to access the lactone-type alkaloid.
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