Chemical Degradation-Inspired Total Synthesis of the Antibiotic Macrodiolide, Luminamicin

Aoi Kimishima, Hiroyasu Ando, Goh Sennari, Yoshihiko Noguchi, Shogo Sekikawa, Toru Kojima, Motoyoshi Ohara, Yoshihiro Watanabe, Yuki Inahashi, Hirokazu Takada, Akihiro Sugawara, Takanori Matsumaru, Masato Iwatsuki, Tomoyasu Hirose, Toshiaki Sunazuka

研究成果: Article査読

2 被引用数 (Scopus)


This article describes the first total synthesis of luminamicin using a strategy combining chemical degradation with synthesis. Chemical degradation studies provided a sense of the inherent reactivity of the natural product, and deconstruction of the molecule gave rise to a key intermediate, which became the target for chemical synthesis. The core structure of the southern part of luminamicin was constructed by a 1,6-oxa-Michael reaction to form an oxa-bridged ring, followed by coupling with a functionalized organolithium species. Modified Shiina macrolactonization conditions forged the strained 10-membered lactone containing a tri-substituted olefin. Diastereoselective α-oxidation of the 10-membered lactone completed the center part to provide the key intermediate. Inspired by the degradation study, an unprecedented enol ether/maleic anhydride moiety was constructed with a one-pot chlorosulfide coupling and thiol β-elimination sequence. Finally, macrolactonization to the 14-membered ring in the presence of the highly electrophilic maleic anhydride moiety was accomplished using modified Mukaiyama reagents to complete the synthesis of luminamicin.

ジャーナルJournal of the American Chemical Society
出版ステータスPublished - 2022 12月 21

ASJC Scopus subject areas

  • 触媒
  • 化学 (全般)
  • 生化学
  • コロイド化学および表面化学


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