Sasaki, Fuwa, and Ebine. JACS, 2006, ASAP. DOI: 10.1021/ja062524q.
Yup, another poly-ether, though with some interesting biological activity; this one seems to have positive effects, increasing tracheal mucus velocity, and thus potentially of use in respiritory disorders. Also, it appears to be a brevetoxin antagonist in vivo. As discussed in the comments surrounding the previous post (ciguatoxin), much of the work relating to ladder-type poly-ethers has been published before, so I’ll stick to the main disconnections.
Firstly, a Suzuki-Miyaura coupling of the main A,B and D,E fragments, building part of the C ring. This was completed using Sasaki’s own methodology involving enol-phosphates:
Completing this coupling in over 84% (quoted over two steps), including a stereoselective hydroboration, they set themselves up nicely to complete the C-ring. Once delivered, they then had to couple the left-hand sidechain, containing a devilsome tetra-substituded olefin. Impressively, they were able to constuct this using a Stille coupling, in its Cu-TC form.
With relatively simple modifications required to complete the right-hand sidechain, they soon delivered the proposed structure for the natural product, but were confronted by ill-matching spectra when compared to the isolated substance. They propose that they have simply made the C-26 epimer of the natural product (the right-most hydroxyl-bearing carbon), so I’m sure we’ll see the complete specimen shortly.