We herein present an efficient and robust synthetic strategy toward 12 icetexane diterpenes and their derivatives, which features a PPh<sub>3</sub>/DIAD-mediated rearrangement of the reduced carnosic acid derivative (<b>2</b>) to give (-)-barbatusol (<b>3</b>) in a regioselective and scalable way. MTT assay led to the identification of (+)-grandione (<b>11</b>) and (-)-demethylsalvicanol <i>o</i>-quinone derivative (<b>9</b>) as highly cytotoxic agents against HCT-116, COLO-205, and Caco-2 cells. Interestingly, (+)-grandione (<b>11</b>) induced the HCT-116 cell apoptosis in a dose-dependent manner, which might be attributed to the upregulation of the BiP-ATF4-CHOP axis and promotion of the BiP-ATF4 interactions, thereby leading to endoplasmic reticulum (ER) stress. This work not only paves an efficient and scalable pathway to access icetexane diterpenes but also provides new leads for the development of anticolorectal agents with a unique mode of action.