Hirama, Inoue, Miyazaki, Ishihara, Tatami, Ohnuma, Kawada, Komano, Yamashita, Lee, and Masahiro . JACS, 2006, ASAP. DOI: 10.1021/ja063041p.
We’re back!! And with a tasty number to start the week with. Or rather not that tasty at all, what with the toxicity of this beast! Originally isolated from four metric tonnes of Moray Eels, at least the eels can breath a sigh of relief that Hirama et al. have finished their total synthesis of Ciguatoxin and its 51-HydroxyCTX3C analogue. Most of the ground work for this synthesis has been published already, including the synthesis of the main fragments, constituting their synthesis of CTX3C.
Starting with the pair of fragments shown above, they formed the S,O acetal directly, and then used that to create the G-ring using an interesting radical cyclisation, which, by using the the correct “protecting group” they were able to derive the correct stereochemistry.
This then set them up for a final RCM to make the 9-member ring-F, and completion of the molecule. Interestingly, they have used the NAP protecting group throughout this project, which seems to be easily removed with DDQ. I’m not sure I’ve seen it used before, but it’s certainly seems useful.
So, a massive effort, and a slightly difficult to read paper (that main scheme is busy); perhaps the eels can sleep easy tonight…
Update: Derek Lowe has a great piece on his blog about the isolation of ciguatoxin.