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

• DOI: 10.1021/jacs.2c10856
• Publication Date: 2022-12-09T17:16:12Z
• Authors: 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
• Keywords: Moiety; Maleic anhydride

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