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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Synthesis of the DEF-Ring Spirocyclic Core of Cyclopamine
Hao Shao1, Wenheng Liu1, Zhengqi Fang1
1Shanghai Key Laboratory of Green Chemistry and Chemical Processes, State Key Laboratory of Petroleum Molecular & Process Engineering, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China.
Abstract:
A stereoselective synthesis of the DEF-ring spirocyclic core of cyclopamine was accomplished using commercially available materials. The key steps in the synthesis were (i) the enantioselective vinylogous Mannich reaction, followed by lactamization to generate the piperidine F ring, and (ii) intramolecular oxidative dearomative spiroetherification to construct the DEF-ring spirocyclic core of cyclopamine. We found that the stereochemistry of the spirocyclization was controlled by the configuration of the methyl group (C-20) in the substrate.
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