18 A Total Synthesis of (±)-Baccatin III utilizing Automated Synthesizers

DOI
  • Doi Takayuki
    Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology
  • Fuse Shinichiro
    Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology
  • Miyamoto Shigeru
    Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology
  • Nakai Kazuoki
    Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology
  • Hirose Yoichiro
    Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology
  • Sasuga Daisuke
    Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology
  • Takahashi Takashi
    Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology

Bibliographic Information

Other Title
  • 18 自動合成ロボットを活用した(±)-Baccatin IIIの全合成(口頭発表の部)

Abstract

In organic synthesis, a plenty of human efforts is necessary to supply synthetic intermediates. The time and energy in simply repeating processes in syntheses can be reduced utilizing automated synthesis apparatus. It is expected that laboratory automation can realize highly efficient, reproducible and safe synthesis of organic compounds. We report here the total synthesis of (±)-baccatin III (2) utilizing automated synthesizers. Initially, the synthetic routes of the A-ring 15 and C-ring 19 from geraniol (11) were established. The all synthetic steps of the A and C-rings were successfully applied to the automated synthesizer by optimizing the reaction conditions adequate to the synthesizer. We also developed the Ti(III)-catalyzed radical cyclization of epoxy-alkene and it was found to be effective as the stoichiometric system previously reported. The synthetic route of the B-ring cyclization precursor 27 from A-ring 15 and C-ring 19 was established. All reactions were accomplished utilizing a high performance solution phase automated synthesizer that we had recently developed. The crucial 8-membered ring formation was effectively assisted by micro-wave irradiation. It was found that the intramolecular alkylation of 27 was accelerated in the presence of excess amount of LiN(TMS)_2. The reaction period was dramatically decreased (10h→15min). Regio- and stereo-selective allylic oxidation and dihydroxylation of exo-alkene provided 30. Oxetane formation without deconjugation of Δ-11 to exo-alkene was crucial. Treatment of 31 with i-Pr_2NEt in HMPA provided the desired 32. After oxidation at 9, 13-positions of 32, we accomplished the total synthesis of (±)-baccatin III (2).

Journal

Details 詳細情報について

  • CRID
    1390282681055500032
  • NII Article ID
    110006682525
  • DOI
    10.24496/tennenyuki.47.0_101
  • ISSN
    24331856
  • Text Lang
    ja
  • Data Source
    • JaLC
    • CiNii Articles
  • Abstract License Flag
    Disallowed

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