Coralloidolides A, B, C, and E
Trauner, Kimbrough, Roethle, Mayer. ACIEE, 2010, EarlyView. DOI: 10.1002/anie.200906126.
It’s not often I get to summarise an entire paper in one scheme, so I’m not. Erm, what I mean to say is that I could, but I think for decencies-sake, I’m going to pad this out a bit! Back in 2006, Dirk Trauner (still at Berkeley back then) completed a rather neat synthesis of Bipinnatin, completing the target in a rather neat nine steps (including a very nice Alder-ene reaction…). This synthesis was actually a means to an entire series, as Bipinnatin can be converted into a whole-load of natural products in a biosynthetic fashion. This was also published in 2006, and resulted in Intricarene (using a 1,3-dipolar cycloaddition), as well as Rubifolide and Isoepilophodione.
This most recent work in Angewantde takes this further, turning Rubifolide into the Coralloidolide family, again using biosynthetic principles. I’m not going into the Bipinnatin J synthesis – that actually goes pre-TotSyn (PTS), but I’ll mention that reduction of that into Rubifolide needs only a little triethylsilane, selectively nuking that pesky hydroxyl in almost quantitative ease. Again, that was published earlier, so to the new stuff – starting with an oxidation. Using that primitive formula of basic peroxide, a nucleophilic epoxiation selectively oxygenates the furanone, entirely diastereoselectively, and yielding the first Coralloidolide, A. Switching to mCPBA, the oxidation action moves to the furan, ring-opening to a 1,4-diketone and generating a rather suspicious-looking ‘dienedione‘ (???). This, amazingly, is a further Coralloidolide – E this time. I’m utterly amazed that this beastie is stable enough to isolate…
Unstable it was – finding reliable conditions for transformation of Coralloidolide E was an effort, with Trauner describing loss of much of their material to ‘a large number of intractable products’, or as I tend to term it, black guff in a flask. Instability is the key, though, as treatment of this with a little scandium triflate (probably quite a long way along the likely-reagents-shelf) resulted in a double trans-annular ring closure, producing a dihydrofuran and a tetrahydro pyran oxepine, along with a pair of stereocenters. Bizarrely, only dioxane (or dioxan as my lab-mates insist on naming it…) is good enough for this reaction – other polar-aprotic solvents such as DMF don’t do the trick. Trauner believes the mechanism is distinctly stepwise, with a hydration of the dienedione first, and then closure onto the epoxide, and that the scandium triflate is required for both steps. Trauner also manages to effect a synthesis of Coralloidolide C, using DBU to perform a transannular aldol reaction on Coralloidolide E, rounding off a rather neat bit of work.
Don’t feel too short-changed by this micro-post; I’m working my way through Overman’s epic Actinophyllic Acid paper this week, and might have it out tomorrow.