Synthetic studies on dimeric monoterpene indole alkaloid: (+) -haplophytine

Since dimeric indole alkaloids possess architectural diversities and a wide range of biological activities, development of new synthetic strategies for construction of these structures has been one of the important topics in synthetic chemistry. Among these compounds, we focused on an architecturally intriguing dimeric monoterpene indole alkaloid, (+) -haplophytine, which had remained an unanswered challenge for more than a quarter century in the area of alkaloid synthesis. Our first total synthesis and the second generation synthesis of (+) -haplophytine are described. The synthesis of this dimeric compound features Ag-mediated coupling reaction between two polycyclic fragments. In addition, the characteristic diazabicyclo [3.3.1] skeleton in left segment was constructed by means of creative skeletal rearrangement including oxidation step.