Synthesis and biological evaluation of a focused library of beauveriolides

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.

A library of beauveriolide analogues focusing on l-Ala and d-allo-Ile of beauveriolide III (1b) was synthesized by combinatorial synthesis and their inhibitory activity of CE synthesis in macrophage was tested. Cyclic compounds 7{1, 3, 2}, 7{2, 3, 1}, and 7{2, 3, 2} were 20 times more potent than 1b.Figure optionsDownload as PowerPoint slide