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Evolution of the Short Enantioselective Total Synthesis of the Unique Marine Myxobacteria Polyketide Salimabromide
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  • Kang-Ji Gan,
  • Yao Zhu,
  • Gaosheng Shi,
  • Changhui Wu,
  • Fu-Qiang Ni,
  • Li-Han Zhao,
  • Xiaowei Dou,
  • Zhihan Zhang,
  • Hai-Hua Lu
Kang-Ji Gan
Zhejiang University
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Yao Zhu
Westlake University
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Gaosheng Shi
Westlake University
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Changhui Wu
China Pharmaceutical University
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Fu-Qiang Ni
Westlake University
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Li-Han Zhao
Westlake University
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Xiaowei Dou
China Pharmaceutical University
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Zhihan Zhang
Central China Normal University
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Hai-Hua Lu
Westlake University

Corresponding Author:luhaihua@westlake.edu.cn

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Abstract

Salimabromide, a unique and scarce marine tetracyclic polyketide, was synthesized in both racemic and optically active forms. A novel carboxylic acid-directed method for tandem oxidative difunctionalization of olefins was developed, whereby the formation of bridged butyrolactone and enone moieties occurs concurrently. Density functional theory (DFT) calculations indicate that this reaction follows a [3+2] process rather than the [2+2] process. In the meantime, the distinctive benzo-fused [4.3.1] carbon skeleton and highly hin-dered vicinal quaternary stereocentres were simultaneously constructed through a challenging intramolecular Giese-Baran radical cyclization. Furthermore, deuterium kinetic isotopic effects were utilized to enhance the efficacy of this pivotal step. This represents a new illustration of the application of kinetic isotope effects in natural product synthesis. Then, short asymmetric syntheses of (+)-salimabromide (13 or 15 steps) was accomplished by combing this method with rhodium-catalyzed enantioselective hydrogena-tion of a cycloheptenone derivative (97% ee) or conjugate addition of an aryl boronic acid with 2-cyclohepten-1-one (> 99% ee).
10 Jul 2024Submitted to Chinese Journal of Chemistry
12 Jul 2024Submission Checks Completed
12 Jul 2024Assigned to Editor
12 Jul 2024Review(s) Completed, Editorial Evaluation Pending
19 Jul 2024Reviewer(s) Assigned
20 Aug 2024Editorial Decision: Revise Minor
06 Sep 20241st Revision Received
06 Sep 2024Submission Checks Completed
06 Sep 2024Assigned to Editor
06 Sep 2024Review(s) Completed, Editorial Evaluation Pending
07 Sep 2024Editorial Decision: Accept