title: Total Synthesis of the 7,10-Epimer of the Proposed Structure of Amphidinolide N, Part I: Synthesis of the C1-C13 Subunit.
abstract: Amphidinolide N, the structure of which has been recently revised, is a 26-membered macrolide featuring allyl epoxide and tetrahydropyran moieties with 13 chiral centers. Due to its challenging structure and extraordinary potent cytotoxicity, amphidinolide N is a highly attractive target of total synthesis. During our total synthesis studies of the 7,10-epimer of the proposed structure of amphidinolide N, we have synthesized the C1-C13 subunit enantio- and diastereoselectively. Key reactions include an l-proline catalyzed enantioselective intramolecular aldol reaction, Evans aldol reaction, Sharpless asymmetric epoxidation and Tamao-Fleming oxidation. To aid late-stage manipulations, we also developed the 4-(N-benzyloxycarbonyl-N-methylamino)butyryl group as a novel ester protective group for the C9 alcohol.
authors: Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan.
authors: Koji
authors: K
authors: Ochiai
authors: Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan.
authors: Sankar
authors: S
authors: Kuppusamy
authors: Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan.
authors: Yusuke
authors: Y
authors: Yasui
authors: Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan.
authors: Tsubasa
authors: T
authors: Okano
authors: Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan.
authors: Yasunobu
authors: Y
authors: Matsumoto
authors: Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan.
authors: Nishant R
authors: NR
authors: Gupta
authors: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
authors: Yohei
authors: Y
authors: Takahashi
authors: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.|Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo, 194-8543, Japan.
authors: Takaaki
authors: T
authors: Kubota
authors: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
authors: Jun'ichi
authors: J
authors: Kobayashi
authors: Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan. yhayashi@m.tohoku.ac.jp.|Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai, 980-8578, Japan. yhayashi@m.tohoku.ac.jp.
authors: Yujiro
authors: Y
authors: Hayashi
keywords: Sharpless epoxidation; Tamao-Fleming oxidation; aldol reaction; organocatalyst; total synthesis