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Concise Enantioselective Total Synthesis of (+)-Punctaporonin U
Paul Gri1, Qian Wang1, Jieping Zhu1
1Laboratory of Synthesis and Natural Products (LSPN), Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, BCH5304, CH-1015 Lausanne, Switzerland.
None:
We report herein the first enantioselective total synthesis of (+)-punctaporonin U, a cage-like pentacyclic sesquiterpene bearing eight contiguous stereocenters. The synthesis features three key transformations: a) a rare cis-selective Mukaiyama-Michael addition of the silyl enol ether derived from 2,2-dimethylcyclobutan-1-one to 4-[(tert-butyldimethylsilyl)oxy]cyclopent-2-en-1-one; b) a domino oxa-Michael addition/aldol reaction/bromination sequence that constructs both a fused five-membered ring and a 1,4-bridged 7-membered ring; c) an intramolecular SN2 displacement to install the 1,3-bridged tetrahydrofuran ring. The synthesis is accomplished in six steps from 4-[(tert-butyldimethylsilyl)oxy]cyclopent-2-en-1-one, which itself is accessible in five steps from cyclopentadiene.
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