Studies towards the total synthesis of Nakadomarin A

Nakadomarin A is a polycyclic marine alkaloid of the manzamine family. It was first isolated from the marine sponge Haliclona sp. collected off Manzamo, (Okinawa, Japan) and was characterised by Kobayashi and co-workers in 1997. The structure of this unprecedented compound was elucidated by exhaustive spectroscopic studies which showed that the natural product has a unique hexacyclic skeleton. In terms of biological activity, this natural product displays cytotoxicity against murine lymphoma L1210 cells (IC50 1.3 μg/mL), inhibitory activity against cyclin-dependent kinase 4 (IC50 9.9 μg/mL), anti-microbial activity against the fungus Trichophyton mentagrophytes (MIC 23 μg/mL) and anti-bacterial activity against the Gram-positive bacterium Corynebacterium xerosis. The complex structure of nakadomarin A combined with its biological activities has made it a highly attractive synthetic target. The work described herein displays the most recent contribution to this field from our research group