A straightforward approach to a novel phytosphingosine-like ceramide has been accomplished. The cornerstone features of this divergent synthesis are a cascade Overman rearrangement of tris(imidate) to introduce three desired stereogenic centres via sequential chirality transfer and an effective olefin cross-metathesis to install a long side chain. The final unusual phytoceramides were evaluated for their capacity to inhibit the proliferation of cancer cell lines. The preliminary results revealed that compound 21 exhibits promising anticancer activity against HeLa and HCT-116 cells as well as the excellent selectivity in cytotoxicity (malignant vs non-malignant cell lines). Display omitted •An approach to a phytosphingosine-like analogue was achieved.•The strategy relied on a cascade rearrangement and OCM reaction.•All stereocentres were installed with the complete chirality transfer.•The target compounds were screened for anticancer activity.