Enantioselective Total Synthesis of (-)-Vinigrol: The Evolution of a Transannular Diels-Alder Strategy
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Updated: Jul 5, 2025

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Published on: November 9, 2019
Xuerong Yu1, Lianghong Xiao1, Tuoping Luo1,2,3
1Key Laboratory of Bioorganic Chemistry and Molecular Engineering, Ministry of Education and Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Abstract:
Vinigrol is a structurally and stereochemically complex diterpenoid that displays various potent pharmacological activities. Two generations of synthetic routes were designed and pursued based on a transannular Diels-Alder (TADA) cycloaddition strategy. An intramolecular [2 + 2]photocycloaddition in the presence of the chelating Lewis acid (MgBr2·Et2O) was first discovered to enable the reaction of sterically challenging substrates, which was followed by [2 + 2]cycloreversion to provide α-pyrones fused with a 10-membered ring. Eventually, a new and scalable synthetic route toward (-)-vinigrol was developed and provided over 600 mg materials, manifesting the power of macrocyclic stereocontrol and TADA reaction.
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