Enantioselective total synthesis of (‒)-lucidumone enabled by tandem prins cyclization/cycloetherification sequence
Xian-Zhang Liao1,2, Ran Wang1,2, Xin Wang1,2
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 100050, Beijing, P. R. China.
Abstract:
The Ganoderma meroterpenoids are a growing class of natural products with architectural complexity, and exhibit a wide range of biological activities. Here, we report an enantioselective total synthesis of the Ganoderma meroterpenoid (‒)-lucidumone. The synthetic route features several key transformations, including a) a Cu-catalyzed enantioselective silicon-tethered intramolecular Diels-Alder cycloaddition to construct the highly functionalized bicyclo[2.2.2]octane moiety; b) Brønsted acid promoted tandem O-deprotection/Prins cyclization/Cycloetherification sequence followed by oxidation to install concurrently the tetrahydrofuran and the fused indanone framework; c) Fleming-Tamao oxidation to generate the secondary hydroxyl; d) an iron-catalyzed Wacker-type oxidation of hindered vinyl group to methyl ketone.
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