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 IC50 values within 1 mu M 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. A concise and collective synthetic route to hypocretenolides was developed for the first time.