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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Structural revision of (+)-uprolide F diacetate confirmed by asymmetric total synthesis
1Department of Chemistry, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong, China.
Abstract:
A new structure for the cytotoxic cembranolide uprolide F diacetate (UFD) was proposed, and an enantioselective total synthesis was accomplished to confirm that our revised structure correctly represented the natural UFD and its absolute configuration. Our synthesis features a late-stage, highly efficient, and diastereoselective Nozaki-Hiyama-Kishi macrocyclization (95% yield) and an unexpected reagent-controlled reversible translactonization, which, being the first example within the cembranolide family, might have biogenetic implications and be of great importance to synthetic studies of the α-methylene-γ-lactone-bearing cembranolides.
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