The total synthesis of the anticancer agent (+)-spisulosine has been accomplished. The strategy involved a substrate-controlled aza-Claisen rearrangement to establish the erythro-configured amino-alcohol motif followed by deoxygenation to create a methyl side-chain. Subsequent Wittig olefination then permitted the construction of the carbon backbone of the target molecule. To investigate the antiproliferative effect of 1, its biological profile was examined on a panel of 6 human malignant cell lines and demonstrated the significant anticancer activity of 1 on at least five of the evaluated lines with IC50 < 1 μM (MCF-7, HTC-116, Caco-2, Jurkat and HeLa).
Keywords: 1-deoxysphingoid bases; Antiproliferative activity; Spisulosine; Stereoselective synthesis; [3,3]-heterosigmatropic rearrangement.
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