Catalytic Asymmetric Amination of N-Nonsubstituted α-Alkoxycarbonyl Amides: Concise Enantioselective Synthesis of Mycestericin F and G

Authors

  • Dr. Farouk Berhal,

    1. Institute of Microbial Chemistry, Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3447-7779
    2. Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
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  • Sho Takechi,

    1. Institute of Microbial Chemistry, Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3447-7779
    2. Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
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  • Dr. Naoya Kumagai,

    Corresponding author
    1. Institute of Microbial Chemistry, Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3447-7779
    2. Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
    • Institute of Microbial Chemistry, Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3447-7779
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  • Prof. Dr. Masakatsu Shibasaki

    Corresponding author
    1. Institute of Microbial Chemistry, Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3447-7779
    2. Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
    • Institute of Microbial Chemistry, Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan), Fax: (+81) 3-3447-7779
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Abstract

In an attempt to explore the synthetic utility of a ternary asymmetric catalyst comprising La(NO3)3⋅6H2O, amide-based ligand (R)-L1, and D-valine tert-butyl ester H-D-Val-OtBu, we investigated a catalytic, asymmetric amination of functionalized N-nonsubstituted α-alkoxycarbonyl amides using di-tert-butyl azodicarboxylate as an electrophilic aminating reagent. A highly functionalized, cyclic N-nonsubstituted α-alkoxycarbonyl amide delivered the desired amination product in up to 96 % enantiometric excess, with the requisite functionalities of the polar heads of sphingosines with the appropriate stereochemical arrangement. The rapid asymmetric assembly of these functional groups allowed a concise enantioselective synthetic route to sphingosines to be established with a broad flexibility towards derivative synthesis. These studies have culminated in an efficient catalytic enantioselective total synthesis of immunosuppressive fungal metabolites mycestericin F (3 a) and G (3 b).

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