Total synthesis and the anticancer activity of (+)-spisulosine

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).