2. Academic Validation
  3. Antimalarial troponoids, puberulic acid and viticolins; divergent synthesis and structure-activity relationship studies

Antimalarial troponoids, puberulic acid and viticolins; divergent synthesis and structure-activity relationship studies

  • Sci Rep. 2017 Aug 3;7(1):7259. doi: 10.1038/s41598-017-07718-3.
Goh Sennari 1,  Ryo Saito 1,  Tomoyasu Hirose 1 2,  Masato Iwatsuki 1 2,  Aki Ishiyama 2,  Rei Hokari 2,  Kazuhiko Otoguro 2,  Satoshi Ōmura 3,  Toshiaki Sunazuka 4 5
Affiliations

Affiliations

  • 1 Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
  • 2 Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
  • 3 Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. omuras@insti.kitasato-u.ac.jp.
  • 4 Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. sunazuka@lisci.kitasato-u.ac.jp.
  • 5 Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. sunazuka@lisci.kitasato-u.ac.jp.
PMID: 28775291 DOI: 10.1038/s41598-017-07718-3
Abstract

Divergent synthesis of antimalarial troponoids, including naturally occurring compounds, some of which were identified and isolated by our group, has been achieved utilizing the total synthetic route of puberulic acid. Structure-activity relationships of Natural Products and simple troponoids inspired us to explore more detailed properties of this class of compounds. Access to new derivatives was facilitated through intermediate compounds generated during the total synthesis of puberulic acid by a stepwise oxidation-aromatization sequence to provide 7-hydroxytropolones and bromination for conversion of the carboxylic acid moiety. The first total synthesis of viticolin A, as well as the synthesis of different methyl-substituted derivatives, has also been achieved. In vitro antimalarial activity and cytotoxicity of novel derivatives were evaluated and fundamental information to facilitate the discovery of more promising antimalarials was obtained.

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