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Divergent Total Synthesis of Tacaman Alkaloids: A Skeleton Reorganization Strategy
Xiao-Feng Guo1, Ya-Kui Sun1, Jin-Bao Qiao1
1Key Laboratory of Applied Surface and Colloid Chemistry of MOE & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an 710119, China.
Abstract:
Herein, we present a divergent synthesis of tacaman alkaloids featuring a pivotal pentacyclic intermediate bearing an exocyclic trisubstituted olefin, accessed via a base-promoted intramolecular cyclopropanation/cyclopropane ring-opening/oxa-Michael cascade and a subsequent electrophilic halomethylation-retro-aza-Michael sequence. This versatile common intermediate enabled the regio- and diastereoselective functionalization of the trisubstituted olefin, affording the total syntheses of tacamonine, tabercamine K, and 19S-hydroxyapotacamine in good yields with excellent stereocontrol. Notably, the Mukaiyama-type hydration reaction was applied to achieve tunable stereochemistry at the C19 and C20 hydroxyl positions.
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