Synthesis and structure–activity relationships for cytotoxicity and apoptosis-inducing activity of (+)-halichonine B

Halichonine B is a sesquiterpene alkaloid isolated from the marine sponge Halichondria okadai Kadota. Halichonine B has exhibited cytotoxicity against mammalian cancer cells and induced apoptosis in the human leukemia cell line HL60. Here we established a practical route for the synthesis of halichonine B and its analogues, and we evaluated their biological activities. It was revealed that the secondary amino groups in the side chain portion are important for the strong cytotoxicity of halichonine B and that the N¹¹-prenyl group is unimportant. Halichonine B and its analogues were also observed to induce apoptosis in HL60 cells.