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Collective Total Synthesis of Englerin A and B, Orientalol E and F, and Oxyphyllol: Application of the Organocatalytic [4+3] Cycloaddition Reaction

Authors

  • Jie Wang,

    1. CAS Key Laboratory of Synthetic Chemistry of Natural, Substances Shanghai, Institute of Organic Chemistry, 345 Lingling Road, 200032 (China), Fax: (+86) 21-54925081
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  • Shu-Guang Chen,

    1. College of Chemistry and Materials Science, Anhui Normal University, Beijing East Road No. 1, Wuhu 241000 (China)
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  • Prof. Dr. Bing-Feng Sun,

    Corresponding author
    1. CAS Key Laboratory of Synthetic Chemistry of Natural, Substances Shanghai, Institute of Organic Chemistry, 345 Lingling Road, 200032 (China), Fax: (+86) 21-54925081
    • CAS Key Laboratory of Synthetic Chemistry of Natural, Substances Shanghai, Institute of Organic Chemistry, 345 Lingling Road, 200032 (China), Fax: (+86) 21-54925081
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  • Prof. Guo-Qiang Lin,

    Corresponding author
    1. CAS Key Laboratory of Synthetic Chemistry of Natural, Substances Shanghai, Institute of Organic Chemistry, 345 Lingling Road, 200032 (China), Fax: (+86) 21-54925081
    • CAS Key Laboratory of Synthetic Chemistry of Natural, Substances Shanghai, Institute of Organic Chemistry, 345 Lingling Road, 200032 (China), Fax: (+86) 21-54925081
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  • Prof. Yong-Jia Shang

    1. College of Chemistry and Materials Science, Anhui Normal University, Beijing East Road No. 1, Wuhu 241000 (China)
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Abstract

The concise collective total synthesis of englerin A and B, orientalol E and F, and oxyphyllol has been accomplished in 10–15 steps, with the total synthesis of orientalol E and oxyphyllol being achieved for the first time. The success obtained was enabled by the realization of the [4+3] cycloaddition reaction of 9 and 10. Other features of the synthesis include 1) the intramolecular Heck reaction to access the azulene core, 2) the epoxidation–SN2′ reduction sequence to access the allylic alcohol, 3) the efficient regioselective and stereoselective formal hydration of the bridging C[DOUBLE BOND]C bond in the synthesis of englerins, and 4) the late-stage chemo- and stereoselective C[BOND]H oxidation in the synthesis of orientalol E. The total synthesis of these natural products has enabled the structural revision of oxyphyllol and established the absolute stereochemical features of the organocatalytic [4+3] cycloaddition reaction. The identification of 5 as the natural product oxyphyllol, the success in converting 5 to orientalol E, along with the fact that englerins and oxyphyllol were isolated from plants of the same genus Phyllanthus gives support to our proposed biosynthetic pathways. This work may enable detailed biological evaluations of these natural products and their analogues and derivatives, especially of their potential in the fight against renal cell carcinoma (RCC).

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