Hypocretenolides: collective total syntheses and activities toward metastatic colon cancer.

A concise and collective synthetic route to hypocretenolides was developed for the first time. This route features one-pot addition-alkylation and intramolecular 1,3-dipolar cycloaddition to efficiently assemble the 5/7/6 ring system. Our syntheses enabled multigram preparation of hypocretenolide which facilitated further biological evaluation. Preliminary CCK-8 cytotoxic results of hypocretenolide indicated its IC 50 values within 1 μM against 4 colon cancer cell lines. Wound healing and transwell assays suggested the promising inhibitory activities of hypocretenolide toward the migratory capabilities of colon cancer cells in vitro . The animal results confirmed that hypocretenolide can inhibit metastasis of colon cancer cells.