著者

Kita Masaki Oka Hirotaka Usui Akihiro Ishitsuka Tomoya Mogi Yuzo Watanabe Hidekazu

出版者

Elsevier

雑誌

Tetrahedron (ISSN:00404020)

巻号頁・発行日

vol.68, no.42, pp.8753-8760, 2012-10

被引用文献数

7

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Mycalolides are tris-oxazole macrolides isolated from the marine sponge Mycale sp., which shows cytotoxic, antifungal, and actin-depolymerizing activities. To develop an efficient synthetic route of mycalolides and to evaluate its functional mechanism of biological activities, tris-oxazole macrolactone analogs of mycalolides were synthesized through the use of ring-closing metathesis (RCM). The presence/absence of protecting groups at C3, solvent polarity, and reaction temperature significantly affected the stereoselectivity of RCM (E/Z=2.5/1.0–1.0/2.5). The 19E- and 19Z-stereoisomers both exhibited moderate cytotoxicity against tumor cells, but neither showed significant actin-depolymerizing properties or antimycotic activity against pathogenic fungi. Thus, both the side-chain (actin-binding) moiety and the macrolactone moiety were suggested to be essential for the potent biological activities of the parent molecules.