Synthesis and biological evaluation of a focused library of beauveriolides

  • Bioorg Med Chem Lett. 2008 Aug 1;18(15):4397-400. doi: 10.1016/j.bmcl.2008.06.054.
Kenichiro Nagai  1 ,  Takayuki Doi ,  Taichi Ohshiro ,  Toshiaki Sunazuka ,  Hiroshi Tomoda ,  Takashi Takahashi ,  Satoshi Omura
Affiliations
  • 1. Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University and The Kitasato Institute, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
PMID: 18620856 DOI: 10.1016/j.bmcl.2008.06.054
Abstract

Fungal beauveriolide III (1b), discovered as an inhibitor of lipid droplet accumulation in mouse macrophages and showing antiatherogenic activity in mouse model, consists of l-Phe, l-Ala, d-allo-Ile, and (3S, 4S)-3-hydroxy-4-methyloctanoic acid moieties. A combinatorial library of beauveriolide analogues focusing on l-Ala and d-allo-Ile of 1b was synthesized by combinatorial synthesis. Among them, d-Ala analogues consisting of A{2} improved their solubility, while those with 7{1,3,2},7{2,3,1}, and 7{2,3,2} were 20 times more potent than 1b.