Abyssomicin C
Nicolaou and Harrison. ACIE, 2006, Early View. DOI: 10.1002/anie.200601116
An interesting approach to the abyssomicin family, this time of the C varient. Without getting into the DMDO-related debacle of the Sorensen and Snider papers (though the discrepency is worth a read!), this is an incredibly popular target. Unsurprising, I guess, due to it’s biological profile, but I’m sure we’ll see a few more syntheses before the year is out.
KC’s route uses an impressive DA to put in the six-member ring, generating two stereocentres, in a process somewhat similar to Ward’s. The reaction goes in an impressive 80% yield, leaving a single diastereoisomer. The five member-ring is then created using a Dieckmann cyclisation, and regioselective epoxide opening. Nice end-game too, using RCM (never!), and, um… some interesting conclusions!
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What was the deal with that dmdo anyway? Both groups used the same method, one gets no product at all, other gets quant? Is some messing around here, or is the dmdo better in princeton?
They are oxidizing two different substrates… Sorensen does the methyl tetronic acid while Snider reports trying the oxidation on the free tetronic acid.
Also, as Snider doesn’t report specific conditions they tried, it’s difficult to say why it didn’t work.
Exactly why I didn’t want to get into it. Still, interesting to see what a marked difference it made. Both routes are really nice, and it would have been difficult to foresee the problems. Such is the way of the total synthesis, I guess. The DA’s are excellent too.
sorensen’s case: vinylogous methyl ester-like (actually, carbonate) FG in substrate
snider’s case: vinylogous acid-like FG in substrate
as a functional group, there is bit of difference between them – especially, the eyes of m-CPBA (only snider reports) are believed to see. on the other hand – please correct me if i’m wrong-, DMDO has been a difficult reagent to rationalize its reactivity pattern (e.g., towards di-, tri-, tetra -substituted olefins).
for the moment, DMDO behaves like m-CPBA; my tentative conclusion.
There’s a LOT of difference in reactivity between them… tetronic acids of this type are extremely acidic… whereas the methyl tetronates aren’t at all. I can imagine some pretty significant confomational differences between the two compounds depending on how the dipoles work out. I do find it surprising that they didn’t try oxidation of the other substrate which they had in hand.
My guess is that Snider got wind of Sorensen’s work and pushed what they had out the door before they got scooped.
That said, both routes are hot.
Excuse my cynicism, but just because they didn’t mention any attempt at oxidising that substrate doesn’t mean they didn’t try it…! Selective publication – the way forward.
interesting point on the conformational outcome, aunt bob.
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