The rich chemical diversity of marine natural products and their useful biological activity has provided a wealth of structures that lend themselves to the discovery of potential drugs. This has been highlighted by the recent introduction of the marine derived painkiller Prialt® and the anti-tumour drug Yondelis®. Among these interesting structures is spiroleucettadine, isolated from the bright yellow, Leucetta calcareous sponge (figure 1) by Crews and co-workers in 2004. The original assigned structure exhibited an unprecedented trans-fused 2-aminoimidazole-oxolane core and also displayed antibacterial activity (6.25 mg/mL against Enterococcus durans).1 The disclosure of spiroleucettadine was met with worldwide interest and soon teams of synthetic chemists set about its total synthesis. Repeated studies2,3,4 showed that the ring closure reaction to afford 1 could not be achieved, which cast doubt on the validity of the originally proposed structure. As a result Crews and co-workers were prompted to re-evaluate the analytical data and ultimately came up with a revised structure 2, which was validated by DFT calculations and X-ray crystallography.5 The seminar discusses our synthetic strategies towards the revised structure of spiroleucettadine 2. This work aims to provide final proof of a contested structure whilst also allowing for biological investigation into structurally unique antibacterials.

Synthetic studies towards spiroleucettadine

251st National Meeting (2016)

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